{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:11:27Z","timestamp":1788948687551,"version":"build-2803163510"},"reference-count":193,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:00:00Z","timestamp":1788912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The immune response of our body, whether it is directed to infective agents, allergens, or tumors, should support our recovery but can also be dangerous if dysregulated. There are molecular systems that have the role of tuning the immune response, such as activating and inhibitory receptors and co-stimulatory molecules. Among this plethora of receptors, immune-checkpoint receptors (ICRs), as well as natural killer receptors (NKRs), expressed on NK and\/or T cells can up- or downregulate the function of activating and inhibitory receptors during immune cell crosstalk. Among NKRs, NKRP1A\/CD161 has shown to be a promising target molecule for immunotherapy. This receptor showed inhibiting or co-stimulatory effects depending on the cell type analyzed as well as the analytical procedures, reagents used, and the experimental context. The aim of the following review will be to explore the structural and functional features of this receptor on immune cells, its relevance in the tumor microenvironment and its targeting as an immunotherapeutic tool in cancers.<\/jats:p>","DOI":"10.3390\/biom16091302","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T09:24:02Z","timestamp":1788945842000},"page":"1302","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["NKR-P1A\/CD161: A Multifunctional Immune Receptor at the Crossroads of Antitumor Immunity"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7696-0794","authenticated-orcid":false,"given":"Chiara Rosa Maria","family":"Uras","sequence":"first","affiliation":[{"name":"Molecular Oncology and Angiogenesis Unit, Azienda Ospedaliera Metropolitana Liguria AOM-IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Taglieri","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Angiogenesis Unit, Azienda Ospedaliera Metropolitana Liguria AOM-IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Di Gregorio","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Angiogenesis Unit, Azienda Ospedaliera Metropolitana Liguria AOM-IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1860-430X","authenticated-orcid":false,"given":"Alessandro","family":"Poggi","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Sperimentale (DIMES), University of Genoa, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/s41577-025-01221-x","article-title":"Regulators of CD8+ T cell exhaustion","volume":"26","author":"Sun","year":"2026","journal-title":"Nat. Rev. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1146\/annurev-immunol-083024-030822","article-title":"Glycan-Binding Proteins in Immunity","volume":"44","author":"Rabinovich","year":"2026","journal-title":"Annu. Rev. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/s41568-025-00893-w","article-title":"Targeting phagocytosis checkpoints for cancer immunotherapy","volume":"26","author":"Veillette","year":"2026","journal-title":"Nat. Rev. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/s41577-025-01208-8","article-title":"Defects in antigen processing and presentation: Mechanisms, immune evasion and implications for cancer vaccine development","volume":"26","author":"Huber","year":"2026","journal-title":"Nat. Rev. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6649314","DOI":"10.1155\/2021\/6649314","article-title":"Similarities between Tumour Immune Response and Chronic Wound Microenvironment: Influence of Mesenchymal Stromal\/Stem Cells","volume":"2021","author":"Peta","year":"2021","journal-title":"J. Immunol. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1146\/annurev-immunol-082724-123843","article-title":"Immune Niches in Cancer","volume":"44","author":"Slingerland","year":"2026","journal-title":"Annu. Rev. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Du, N., Zhang, K., Guo, J., Yan, W., and Xu, L. (2026). From mucus secretion to immune surveillance: The evolving roles of goblet cells in intestinal homeostasis and inflammation. Front. Immunol., 17.","DOI":"10.3389\/fimmu.2026.1735230"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s41232-026-00422-8","article-title":"Tissue-resident memory T cells in organ transplantation: Implications for immune homeostasis and graft outcomes","volume":"46","author":"Li","year":"2026","journal-title":"Inflamm. Regen."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/imm.70036","article-title":"The Immune System and Cellular Senescence: A Complex Interplay in Aging and Disease","volume":"177","author":"Ayoub","year":"2026","journal-title":"Immunology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1093\/neuonc\/noag003","article-title":"Tumor microenvironment shapes the spatial organization of glioblastoma cell states","volume":"28","author":"Prakash","year":"2026","journal-title":"Neuro Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2602715","DOI":"10.1080\/08916934.2025.2602715","article-title":"Regulation of intestinal regulatory T cells via stress response pathways in inflammatory bowel disease","volume":"59","author":"Alula","year":"2026","journal-title":"Autoimmunity"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.immuni.2026.02.017","article-title":"Cellular memory of sub-lethal stress","volume":"59","author":"Tait","year":"2026","journal-title":"Immunity"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"115986","DOI":"10.1016\/j.intimp.2025.115986","article-title":"Immune escape in colorectal cancer: Mechanisms and challenges of immune checkpoint inhibitor resistance","volume":"169","author":"Yousefi","year":"2026","journal-title":"Int. Immunopharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s12282-025-01793-5","article-title":"Immune checkpoint inhibition in breast cancer: Targeting PD-1\/PD-L1 pathway for therapeutic advances","volume":"33","author":"Shin","year":"2026","journal-title":"Breast Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/s41575-025-01127-y","article-title":"WNT\u2013\u03b2-catenin signalling in hepatocellular carcinoma: From bench to clinical trials","volume":"23","author":"Lehrich","year":"2026","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1186\/s12943-026-02609-6","article-title":"Precision immunotherapy for head and neck cancer: Therapeutic combinations, biomarker strategies, and translational challenges","volume":"25","author":"Okuyama","year":"2026","journal-title":"Mol. Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1158\/1078-0432.CCR-25-2846","article-title":"Efficacy of Immune Checkpoint Inhibitors and Oncoviruses in Solid Tumors","volume":"32","author":"Mechahougui","year":"2026","journal-title":"Clin. Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/s41577-025-01218-6","article-title":"Targeting MHC-E as a new strategy for vaccines and immunotherapeutics","volume":"26","author":"Borrow","year":"2026","journal-title":"Nat. Rev. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1146\/annurev-immunol-083024-025659","article-title":"Targeting of Inhibitory Immune Receptors in Inflammatory Disease Guided by Molecular Understanding of Their Function","volume":"44","author":"Meyaard","year":"2026","journal-title":"Annu. Rev. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e20634","DOI":"10.1002\/advs.202520634","article-title":"T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities","volume":"13","author":"Yu","year":"2026","journal-title":"Adv. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1158\/1078-0432.CCR-25-0447","article-title":"The CD94\/NKG2A\u2013HLA-E Axis as a Target in Cancer Immunotherapy: A Critical Perspective","volume":"32","author":"Vilches","year":"2026","journal-title":"Clin. Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.omto.2021.11.016","article-title":"Natural killer cells and immune-checkpoint inhibitor therapy: Current knowledge and new challenges","volume":"24","author":"Poggi","year":"2022","journal-title":"Mol. Ther. Oncolytics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e1425\u201334","DOI":"10.1093\/oncolo\/oyae134","article-title":"Safety, efficacy, and survival outcomes of immune checkpoint inhibitors rechallenge in patients with cancer: A systematic review and meta-analysis","volume":"29","author":"Liu","year":"2024","journal-title":"Oncologist"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"103121","DOI":"10.1016\/j.ctrv.2026.103121","article-title":"Hematological immune-related adverse events associated with checkpoint inhibitors","volume":"145","author":"Janson","year":"2026","journal-title":"Cancer Treat. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Kang, J.H. (2026). Evolution of Immune Checkpoint Blockade in Metastatic NSCLC: A Narrative Review of Emerging Bispecific Antibodies and the Practical Challenges of Clinical Integration. Cancers, 18.","DOI":"10.3390\/cancers18040709"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e71888","DOI":"10.1002\/cam4.71888","article-title":"A Systematic Review and Meta-Analysis of the Impact of Tumour Mutation Burden on Survival Outcomes in Solid Tumours","volume":"15","author":"Meng","year":"2026","journal-title":"Cancer Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.immuni.2025.11.021","article-title":"Immune signature-based uncoupling of checkpoint inhibitor efficacy and toxicity","volume":"59","author":"Lucas","year":"2026","journal-title":"Immunity"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"152454","DOI":"10.1016\/j.seminoncol.2025.152454","article-title":"Immuno-oncology approaches to overcome T cell exhaustion in melanoma","volume":"53","author":"Alshahrani","year":"2026","journal-title":"Semin. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"126848","DOI":"10.1016\/j.ijpharm.2026.126848","article-title":"From T cells to NK cells and macrophages: Progress and challenges in CAR-based therapies and the involved gene delivery systems","volume":"696","author":"Guerreiro","year":"2026","journal-title":"Int. J. Pharm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.it.2026.01.009","article-title":"Molecular determinants of NK cell memory","volume":"47","author":"Owyong","year":"2026","journal-title":"Trends Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s41577-025-01219-5","article-title":"Metabolic control of innate-like T cells","volume":"26","author":"Riffelmacher","year":"2026","journal-title":"Nat. Rev. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Ustiuzhanina, M.O., Kovalenko, E.I., and Chudakov, D.M. (2026). Post-translational modification of NK cell receptors offers clues to antigenic specificity riddle. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1671844"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e3","DOI":"10.4110\/in.2026.26.e3","article-title":"Integrative Roles of NK Receptors and \u03b3\u03b4 TCRs in \u03b3\u03b4 T Cell-Mediated Cancer Immunity","volume":"26","author":"Oh","year":"2026","journal-title":"Immune Netw."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1080\/1744666X.2026.2621811","article-title":"CAR-T cell immunotherapy of malignant melanoma","volume":"22","author":"Kharasakhal","year":"2026","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1146\/annurev-immunol-083024-030412","article-title":"CD8+ Regulatory T Cells","volume":"44","author":"Vuttaradhi","year":"2026","journal-title":"Annu. Rev. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/j.coi.2008.07.004","article-title":"Role of KIRs and KIR ligands in hematopoietic transplantation","volume":"20","author":"Velardi","year":"2008","journal-title":"Curr. Opin. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.smim.2008.06.003","article-title":"The Yin and Yang of HLA and KIR in human disease","volume":"20","author":"Kulkarni","year":"2008","journal-title":"Semin. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"101568","DOI":"10.1016\/j.beha.2024.101568","article-title":"Interfering with KIR and NKG2A immune checkpoint axes to unleash NK cell immunotherapy","volume":"37","author":"Beelen","year":"2024","journal-title":"Best Pract. Res. Clin. Haematol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.molimm.2004.07.027","article-title":"Immunogenetics of killer cell immunoglobulin-like receptors","volume":"42","author":"Parham","year":"2005","journal-title":"Mol. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1111\/imr.12316","article-title":"Human KIR repertoires: Shaped by genetic diversity and evolution","volume":"267","author":"Manser","year":"2015","journal-title":"Immunol. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.4049\/jimmunol.176.4.2397","article-title":"CD161 (Human NKR-P1A) Signaling in NK Cells Involves the Activation of Acid Sphingomyelinase","volume":"176","author":"Pozo","year":"2006","journal-title":"J. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3463","DOI":"10.3390\/molecules20023463","article-title":"Nkrp1 Family, from Lectins to Protein Interacting Molecules","volume":"20","author":"Ivanova","year":"2015","journal-title":"Molecules"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1002\/eji.1830260613","article-title":"Expression of human NKRP1A by CD34 + immature thymocytes: NKRP1A-mediated regulation of proliferation and cytolytic activity","volume":"26","author":"Poggi","year":"1996","journal-title":"Eur. J. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6071","DOI":"10.4049\/jimmunol.168.12.6071","article-title":"Transendothelial Migratory Pathways of V\u03b41+TCR\u03b3\u03b4+ and V\u03b42+TCR\u03b3\u03b4+ T Lymphocytes from Healthy Donors and Multiple Sclerosis Patients: Involvement of Phosphatidylinositol 3 Kinase and Calcium Calmodulin-Dependent Kinase II","volume":"168","author":"Poggi","year":"2002","journal-title":"J. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.4049\/jimmunol.153.6.2417","article-title":"Human NKR-P1A. A disulfide-linked homodimer of the C-type lectin superfamily expressed by a subset of NK and T lymphocytes","volume":"153","author":"Lanier","year":"1994","journal-title":"J. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"6179","DOI":"10.1111\/j.1742-4658.2005.05031.x","article-title":"The C-type lectin-like domain superfamily","volume":"272","author":"Zelensky","year":"2005","journal-title":"FEBS J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.3390\/ijms15011271","article-title":"Re-Evaluation of Binding Properties of Recombinant Lymphocyte Receptors NKR-P1A and CD69 to Chemically Synthesized Glycans and Peptides","volume":"15","author":"Prchal","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/nri1055","article-title":"Immune functions encoded by the natural killer gene complex","volume":"3","author":"Yokoyama","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Bartel, Y., Bauer, B., and Steinle, A. (2013). Modulation of NK Cell Function by Genetically Coupled C-Type Lectin-Like Receptor\/Ligand Pairs Encoded in the Human Natural Killer Gene Complex. Front. Immunol., 4.","DOI":"10.3389\/fimmu.2013.00362"},{"key":"ref_50","first-page":"187","article-title":"Trial Watch","volume":"3","author":"Bell","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5100","DOI":"10.1073\/pnas.0913108107","article-title":"Interaction of C-type lectin-like receptors NKp65 and KACL facilitates dedicated immune recognition of human keratinocytes","volume":"107","author":"Spreu","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1038\/ni1402","article-title":"Mutual activation of natural killer cells and monocytes mediated by NKp80-AICL interaction","volume":"7","author":"Welte","year":"2006","journal-title":"Nat. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1007\/s002510050294","article-title":"Structure and diversity of the heavy chain VDJ junctions in the developing Mexican axolotl","volume":"46","author":"Golub","year":"1997","journal-title":"Immunogenetics"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1007\/s002510050276","article-title":"The human natural killer gene complex is located on chromosome 12p12-p13","volume":"46","author":"Renedo","year":"1997","journal-title":"Immunogenetics"},{"key":"ref_55","unstructured":"Poggi, A., Revello, V., Nanni, L., Costa, P., and Moretta, L. (1997). Leukocyte Typing VI, White Cell Differentiation Antigens, Garland Publishing Inc.. CD161 (Human NKR-P1A) Workshop Panel Report."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1038\/ni954","article-title":"Genetically linked C-type lectin-related ligands for the NKRP1 family of natural killer cell receptors","volume":"4","author":"Iizuka","year":"2003","journal-title":"Nat. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jim.2004.08.008","article-title":"CD107a as a functional marker for the identification of natural killer cell activity","volume":"294","author":"Alter","year":"2004","journal-title":"J. Immunol. Methods"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"7791","DOI":"10.4049\/jimmunol.175.12.7791","article-title":"Cutting Edge: Lectin-Like Transcript 1 Is a Ligand for the CD161 Receptor","volume":"175","author":"Aldemir","year":"2005","journal-title":"J. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1093\/intimm\/9.9.1271","article-title":"P40 molecule regulates NK cell activation mediated by NK receptors for HLA class I antigens and TCR-mediated triggering of T lymphocytes","volume":"9","author":"Poggi","year":"1997","journal-title":"Int. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Gonzalez, Y., Herrera, M.T., Ju\u00e1rez, E., Salazar-Lezama, M.A., Bobadilla, K., and Torres, M. (2015). CD161 Expression Defines a Th1\/Th17 Polyfunctional Subset of Resident Memory T Lymphocytes in Bronchoalveolar Cells. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0123591"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Shen, H., Zhang, W., Abraham, C., and Cho, J.H. (2013). Age and CD161 Expression Contribute to Inter-Individual Variation in Interleukin-23 Response in CD8+ Memory Human T Cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0057746"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Konduri, V., Oyewole-Said, D., Vazquez-Perez, J., Weldon, S.A., Halpert, M.M., Levitt, J.M., and Decker, W.K. (2021). CD8+CD161+ T-Cells: Cytotoxic Memory Cells With High Therapeutic Potential. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.613204"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e003995","DOI":"10.1136\/jitc-2021-003995","article-title":"CD161 expression and regulation defines rapidly responding effector CD4+ T cells associated with improved survival in HPV16-associated tumors","volume":"10","author":"Duurland","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1002\/hep.22040","article-title":"CD161 expression on hepatitis C virus\u2013specific CD8+ T cells suggests a distinct pathway of T cell differentiation","volume":"47","author":"Northfield","year":"2008","journal-title":"Hepatology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/mi.2015.69","article-title":"CD161intCD8+ T cells: A novel population of highly functional, memory CD8+ T cells enriched within the gut","volume":"9","author":"Fergusson","year":"2016","journal-title":"Mucosal Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Fergusson, J.R., Fleming, V.M., and Klenerman, P. (2011). CD161-Expressing Human T Cells. Front. Immunol., 2.","DOI":"10.3389\/fimmu.2011.00036"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"211","DOI":"10.4049\/jimmunol.176.1.211","article-title":"Expression of CD161 (NKR-P1A) Defines Subsets of Human CD4 and CD8 T Cells with Different Functional Activities","volume":"176","author":"Takahashi","year":"2006","journal-title":"J. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/j.1752-8062.2011.00300.x","article-title":"Prostaglandin E2 and IL-23 plus IL-1\u03b2 Differentially Regulate the Th1\/Th17 Immune Response of Human CD161+CD4+ Memory T Cells","volume":"4","author":"Barrie","year":"2011","journal-title":"Clin. Transl. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Rodriguez, M.W., Paquet, A.C., Yang, Y.H., and Erle, D.J. (2004). Differential gene expression by integrin \u03b27+ and \u03b27\u2212 memory T helper cells. BMC Immunol., 5.","DOI":"10.1186\/1471-2172-5-13"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.molimm.2003.11.004","article-title":"Degenerate recognition of T cell epitopes: Impact of T cell receptor reserve and stability of peptide:MHC complexes","volume":"40","author":"Ford","year":"2004","journal-title":"Mol. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1002\/jcb.1107","article-title":"Differentially induced expression of C-type lectins in activated lymphocytes","volume":"81","author":"Eichler","year":"2001","journal-title":"J. Cell. Biochem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1002\/jlb.62.6.741","article-title":"Rat monocytes up-regulate NKR-P1A and down-modulate CD4 and CD43 during activation in vivo: Monocyte subpopulations in normal and IFN-\u03b3-treated rats","volume":"62","author":"Scriba","year":"1997","journal-title":"J. Leukoc. Biol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"5022","DOI":"10.1038\/s41467-022-32577-6","article-title":"Structure of the human NK cell NKR-P1:LLT1 receptor:Ligand complex reveals clustering in the immune synapse","volume":"13","author":"Cmunt","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1385\/IR:35:1:13","article-title":"NKR-P1 Biology: From Prototype to Missing Self","volume":"35","author":"Mesci","year":"2006","journal-title":"Immunol. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s00251-011-0520-1","article-title":"Phylogenetic and functional conservation of the NKR-P1F and NKR-P1G receptors in rat and mouse","volume":"63","author":"Kveberg","year":"2011","journal-title":"Immunogenetics"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1007\/s00894-010-0837-y","article-title":"Structural analysis of natural killer cell receptor protein 1 (NKR-P1) extracellular domains suggests a conserved long loop region involved in ligand specificity","volume":"17","author":"Pazderka","year":"2011","journal-title":"J. Mol. Model."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Ad\u00e1mkov\u00e1, L., Kv\u00ed\u010dalov\u00e1, Z., Rozbesk\u00fd, D., Kuka\u010dka, Z., Ad\u00e1mek, D., Cebecauer, M., and Nov\u00e1k, P. (2019). Oligomeric Architecture of Mouse Activating Nkrp1 Receptors on Living Cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20081884"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.coi.2007.11.002","article-title":"Immune evasion of natural killer cells by viruses","volume":"20","year":"2008","journal-title":"Curr. Opin. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e202451562","DOI":"10.1002\/eji.202451562","article-title":"Adaptive NKG2C+ NK cells in cytomegalovirus seropositive individuals predominantly lack NKR-P1A receptor expression","volume":"55","author":"Alkassab","year":"2025","journal-title":"Eur. J. Immunol."},{"key":"ref_80","first-page":"77","article-title":"Extending missing-self? Functional interactions between lectin-like NKrp1 receptors on NK cells with lectin-like ligands","volume":"298","author":"Plougastel","year":"2006","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1002\/eji.200838891","article-title":"Two major groups of rat NKR-P1 receptors can be distinguished based on chromosomal localization, phylogenetic analysis and Clr ligand binding","volume":"39","author":"Kveberg","year":"2009","journal-title":"Eur. J. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.3727\/096368913X670930","article-title":"The role of alloresponsive Ly49+ NK cells in rat islet allograft failure in the presence and absence of cytomegalovirus","volume":"23","author":"Smelt","year":"2014","journal-title":"Cell Transplant."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/j.immuni.2007.03.013","article-title":"Cytomegalovirus evasion of innate immunity by subversion of the NKR-P1B:Clr-b missing-self axis","volume":"26","author":"Voigt","year":"2007","journal-title":"Immunity"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Kirkham, C.L., and Carlyle, J.R. (2014). Complexity and Diversity of the NKR-P1:Clr (Klrb1:Clec2) Recognition Systems. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00214"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"4789","DOI":"10.4049\/jimmunol.174.8.4789","article-title":"Functional Requirements for Signaling through the Stimulatory and Inhibitory Mouse NKR-P1 (CD161) NK Cell Receptors","volume":"174","author":"Ljutic","year":"2005","journal-title":"J. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1002\/eji.200940257","article-title":"CD161 is a marker of all human IL-17-producing T-cell subsets and is induced by RORC","volume":"40","author":"Maggi","year":"2010","journal-title":"Eur. J. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1084\/jem.20080397","article-title":"Human interleukin 17\u2013producing cells originate from a CD161+CD4+ T cell precursor","volume":"205","author":"Cosmi","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1159\/000330903","article-title":"Higher frequencies of CD161+ circulating T lymphocytes in allergic rhinitis patients compared to healthy donors","volume":"158","author":"Poggi","year":"2012","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1097\/ACI.0000000000000310","article-title":"A systematic review of the role of interleukin-17 and the interleukin-20 family in inflammatory allergic skin diseases","volume":"16","author":"Hofmann","year":"2016","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41392-023-01620-3","article-title":"The IL-17 family in diseases: From bench to bedside","volume":"8","author":"Huangfu","year":"2023","journal-title":"Signal Transduct. Target Ther."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1111\/j.1365-3083.2007.01920.x","article-title":"Treatment with anti-TNF \u03b1 does not induce reactivation of latent Salmonella enterica serovar Typhimurium infection in C3H\/HeN mice","volume":"65","author":"Martina","year":"2007","journal-title":"Scand. J. Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1111\/j.1365-3083.2006.01885.x","article-title":"Peripheral Blood CD161+ T Cells from Asthmatic Patients are Activated During Asthma Attack and Predominantly Produce IFN-\u03b3","volume":"65","author":"Vaughan","year":"2007","journal-title":"Scand. J. Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"6901","DOI":"10.1158\/1078-0432.CCR-06-0977","article-title":"Increased Frequency of CD4+ Cells Expressing CD161 in Cancer Patients","volume":"12","author":"Iliopoulou","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1158\/2326-6066.CIR-22-0454","article-title":"CD161 Characterizes an Inflamed Subset of Cytotoxic T Lymphocytes Associated with Prolonged Survival in Human Papillomavirus\u2013Driven Oropharyngeal Cancer","volume":"11","author":"Wei","year":"2023","journal-title":"Cancer Immunol. Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"e008694","DOI":"10.1136\/jitc-2023-008694","article-title":"Poor clinical outcomes and immunoevasive contexture in CD161+CD8+ T cells barren human pancreatic cancer","volume":"12","author":"Chen","year":"2024","journal-title":"J. Immunother. Cancer"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1007\/s101470200004","article-title":"Establishment of an immortalized T-cell line from lung cancer tissue: Phenotypic and functional analyses","volume":"7","author":"Imahayashi","year":"2002","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1158\/1078-0432.CCR-18-1749","article-title":"The Anatomical Location Shapes the Immune Infiltrate in Tumors of Same Etiology and Affects Survival","volume":"25","author":"Santegoets","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2887","DOI":"10.1084\/jem.20172021","article-title":"SOX4 controls invariant NKT cell differentiation by tuning TCR signaling","volume":"215","author":"Malhotra","year":"2018","journal-title":"J. Exp. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1111\/cas.15236","article-title":"Clinical characterization and immunosuppressive regulation of CD161 (KLRB1) in glioma through 916 samples","volume":"113","author":"Di","year":"2022","journal-title":"Cancer Sci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1016\/j.cell.2021.01.022","article-title":"Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis","volume":"184","author":"Mathewson","year":"2021","journal-title":"Cell"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1038\/nm.3909","article-title":"The prognostic landscape of genes and infiltrating immune cells across human cancers","volume":"21","author":"Gentles","year":"2015","journal-title":"Nat. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e15654","DOI":"10.7717\/peerj.15654","article-title":"The prognostic significance of KLRB1 and its further association with immune cells in breast cancer","volume":"11","author":"Xu","year":"2023","journal-title":"PeerJ"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"13265","DOI":"10.18632\/aging.205239","article-title":"Inhibiting KLRB1 expression is associated with impairing cancer immunity and leading to cancer progression and poor prognosis in breast invasive carcinoma patients","volume":"15","author":"He","year":"2023","journal-title":"Aging"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.cell.2020.11.041","article-title":"Single-cell landscape of the ecosystem in early-relapse hepatocellular carcinoma","volume":"184","author":"Sun","year":"2021","journal-title":"Cell"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Fang, S., and Zhou, Y. (2024). Deciphering the role of KLRB1: A novel prognostic indicator in hepatocellular carcinoma. BMC Gastroenterol., 24.","DOI":"10.1186\/s12876-024-03299-4"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"36207","DOI":"10.1074\/jbc.M110.179622","article-title":"Characterization of Alternatively Spliced Transcript Variants of CLEC2D Gene","volume":"285","author":"Germain","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"23823","DOI":"10.1074\/jbc.M110.214254","article-title":"Molecular Basis for LLT1 Protein Recognition by Human CD161 Protein (NKRP1A\/KLRB1)","volume":"286","author":"Kamishikiryo","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"6508","DOI":"10.4049\/jimmunol.180.10.6508","article-title":"Functional Consequences of Interactions between Human NKR-P1A and Its Ligand LLT1 Expressed on Activated Dendritic Cells and B Cells","volume":"180","author":"Rosen","year":"2008","journal-title":"J. Immunol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.4049\/jimmunol.1502462","article-title":"LLT1 and CD161 Expression in Human Germinal Centers Promotes B Cell Activation and CXCR4 Downregulation","volume":"196","author":"Llibre","year":"2016","journal-title":"J. Immunol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"3527","DOI":"10.1073\/pnas.0308304101","article-title":"Missing self-recognition of Ocil\/Clr-b by inhibitory NKR-P1 natural killer cell receptors","volume":"101","author":"Carlyle","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"37964","DOI":"10.1074\/jbc.M111.285312","article-title":"Induction of Lectin-like Transcript 1 (LLT1) Protein Cell Surface Expression by Pathogens and Interferon-\u03b3 Contributes to Modulate Immune Responses","volume":"286","author":"Germain","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"68650","DOI":"10.18632\/oncotarget.11896","article-title":"Overexpression of LLT1 (OCIL, CLEC2D) on prostate cancer cells inhibits NK cell-mediated killing through LLT1-NKRP1A (CD161) interaction","volume":"7","author":"Mathew","year":"2016","journal-title":"Oncotarget"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Buller, C.W., Mathew, P.A., and Mathew, S.O. (2020). Roles of NK Cell Receptors 2B4 (CD244), CS1 (CD319), and LLT1 (CLEC2D) in Cancer. Cancers, 12.","DOI":"10.3390\/cancers12071755"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Braud, V.M., Meghraoui-Kheddar, A., Elaldi, R., Petti, L., Germain, C., and Anju\u00e8re, F. (2022). LLT1-CD161 Interaction in Cancer: Promises and Challenges. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.847576"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1007\/s11060-024-04750-y","article-title":"Correlation of LLT-1 and NLRC4 inflammasome and its effect on glioblastoma prognosis","volume":"169","author":"Park","year":"2024","journal-title":"J. Neurooncol"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/s41408-024-01199-0","article-title":"Single-cell transcriptomic and spatial analysis reveal the immunosuppressive microenvironment in relapsed\/refractory angioimmunoblastic T-cell lymphoma","volume":"14","author":"Zhu","year":"2024","journal-title":"Blood Cancer J."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"e008667","DOI":"10.1136\/jitc-2023-008667","article-title":"Single-cell analysis reveals cellular and molecular factors counteracting HPV-positive oropharyngeal cancer immunotherapy outcomes","volume":"12","author":"Cha","year":"2024","journal-title":"J. Immunother. Cancer"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Mandal, T., Gnanasegaran, S., Rodrigues, G., Kashipathi, S., Tiwari, A., Dubey, A.K., Bhattacharjee, S., Manjunath, Y., Krishna, S., and Madhusudhan, M.S. (2024). Targeting LLT1 as a potential immunotherapy option for cancer patients non-responsive to existing checkpoint therapies in multiple solid tumors. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-13074-z"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"715","DOI":"10.4049\/jimmunol.1700387","article-title":"A Role of NKR-P1A (CD161) and Lectin-like Transcript 1 in Natural Cytotoxicity against Human Articular Chondrocytes","volume":"200","author":"Bocian","year":"2018","journal-title":"J. Immunol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1182\/blood.2023022882","article-title":"Targeting of the CD161 inhibitory receptor enhances T-cell\u2013mediated immunity against hematological malignancies","volume":"143","author":"Kang","year":"2024","journal-title":"Blood"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"6437057","DOI":"10.1155\/2020\/6437057","article-title":"Research Progress on NK Cell Receptors and Their Signaling Pathways","volume":"2020","author":"Chen","year":"2020","journal-title":"Mediat. Inflamm."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"7796","DOI":"10.4049\/jimmunol.175.12.7796","article-title":"Cutting Edge: Lectin-Like Transcript-1 Is a Ligand for the Inhibitory Human NKR-P1A Receptor","volume":"175","author":"Rosen","year":"2005","journal-title":"J. Immunol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"2454","DOI":"10.1002\/eji.1830231012","article-title":"CD45-mediated regulation of LFA1 function in human natural killer cells. Anti-CD45 monoclonal antibodies inhibit the calcium mobilization induced via LFA1 molecules","volume":"23","author":"Poggi","year":"1993","journal-title":"Eur. J. Immunol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1111\/j.1600-065X.1982.tb01064.x","article-title":"LFA-1 and Lyt-2,3, Molecules Associated with T Lymphocyte-Mediated Killing; and Mac-1, an LFA-1 Homologue Associated with Complement Receptor Function 1","volume":"68","author":"Springer","year":"1982","journal-title":"Immunol. Rev."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Guerra-Espinosa, C., Jim\u00e9nez-Fern\u00e1ndez, M., S\u00e1nchez-Madrid, F., and Serrador, J.M. (2024). ICAMs in Immunity, Intercellular Adhesion and Communication. Cells, 13.","DOI":"10.3390\/cells13040339"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"5779","DOI":"10.4049\/jimmunol.154.11.5779","article-title":"Functional ambivalence of the Kp43 (CD94) NK cell-associated surface antigen","volume":"154","author":"Melero","year":"1995","journal-title":"J. Immunol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/j.1600-065X.1991.tb00590.x","article-title":"Molecular and Cellular Analysis of Human T Lymphocytes Expressing \u03b3\u03b4 T-Cell Receptor","volume":"120","author":"Morctta","year":"1991","journal-title":"Immunol. Rev."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1084\/jem.174.6.1393","article-title":"CD69-mediated pathway of lymphocyte activation: Anti-CD69 monoclonal antibodies trigger the cytolytic activity of different lymphoid effector cells with the exception of cytolytic T lymphocytes expressing T cell receptor alpha\/beta","volume":"174","author":"Moretta","year":"1991","journal-title":"J. Exp. Med."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0198-8859(99)00162-7","article-title":"The human natural cytotoxicity receptors (NCR) that induce HLA class I-independent NK cell triggering","volume":"61","author":"Bottino","year":"2000","journal-title":"Hum. Immunol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"4098","DOI":"10.1182\/blood-2002-04-1284","article-title":"Soluble HLA class I induces NK cell apoptosis upon the engagement of killer-activating HLA class I receptors through FasL-Fas interaction","volume":"100","author":"Spaggiari","year":"2002","journal-title":"Blood"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1084\/jem.172.6.1589","article-title":"Identification of four subsets of human CD3-CD16+ natural killer (NK) cells by the expression of clonally distributed functional surface molecules: Correlation between subset assignment of NK clones and ability to mediate specific alloantigen recognition","volume":"172","author":"Moretta","year":"1990","journal-title":"J. Exp. Med."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Pende, D., Falco, M., Vitale, M., Cantoni, C., Vitale, C., Munari, E., Bertaina, A., Moretta, F., Del Zotto, G., and Pietra, G. (2019). Killer Ig-Like Receptors (KIRs): Their Role in NK Cell Modulation and Developments Leading to Their Clinical Exploitation. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01179"},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Poggi, A., Matis, S., Uras, C.R.M., Raffaghello, L., Benelli, R., and Zocchi, M.R. (2025). The Role of LAIR1 as a Regulatory Receptor of Antitumor Immune Cell Responses and Tumor Cell Growth and Expansion. Biomolecules, 15.","DOI":"10.3390\/biom15060866"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1093\/intimm\/7.4.697","article-title":"Cytolytic T lymphocytes displaying natural killer (NK)-like activity: Expression of NK-related functional receptors for HLA class I molecules (p58 and CD94) and inhibitory effect on the TCR-mediated target cell lysis or lymphokine production","volume":"7","author":"Mingari","year":"1995","journal-title":"Int. Immunol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1002\/(SICI)1521-4141(199805)28:05<1611::AID-IMMU1611>3.0.CO;2-6","article-title":"IL-12-induced up-regulation of NKRP1A expression in human NK cells and consequent NKRP1A- mediated down-regulation of NK cell activation","volume":"289","author":"Poggi","year":"1998","journal-title":"Eur. J. Immunol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1845","DOI":"10.1084\/jem.184.5.1845","article-title":"Definition of a natural killer NKR-P1A+\/CD56-\/CD16- functionally immature human NK cell subset that differentiates in vitro in the presence of interleukin 12","volume":"184","author":"Bennett","year":"1996","journal-title":"J. Exp. Med."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"3987","DOI":"10.1182\/blood-2011-09-379693","article-title":"Human NK cells at early stages of differentiation produce CXCL8 and express CD161 molecule that functions as an activating receptor","volume":"119","author":"Montaldo","year":"2012","journal-title":"Blood"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.1073\/pnas.1016257108","article-title":"CD34+ hematopoietic precursors are present in human decidua and differentiate into natural killer cells upon interaction with stromal cells","volume":"108","author":"Vacca","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"4052","DOI":"10.1182\/blood-2010-09-303081","article-title":"Development of IL-22\u2013producing NK lineage cells from umbilical cord blood hematopoietic stem cells in the absence of secondary lymphoid tissue","volume":"117","author":"Tang","year":"2011","journal-title":"Blood"},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Poto, R., Cristinziano, L., Modestino, L., de Paulis, A., Marone, G., Loffredo, S., Galdiero, M.R., and Varricchi, G. (2022). Neutrophil Extracellular Traps, Angiogenesis and Cancer. Biomedicines, 10.","DOI":"10.3390\/biomedicines10020431"},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Sok\u00f3lska, W., Gudowska-Sawczuk, M., and Orywal, K. (2026). Cytokines and Chemokines as Emerging Biomarkers and Therapeutic Targets in Colorectal Cancer\u2014Narrative Review. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27041996"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1084\/jem.188.5.867","article-title":"CD161 (NKR-P1A) Costimulation of CD1d-dependent Activation of Human T Cells Expressing Invariant V\u03b124J\u03b1Q T Cell Receptor \u03b1 Chains","volume":"188","author":"Exley","year":"1998","journal-title":"J. Exp. Med."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1084\/jem.182.2.459","article-title":"CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation","volume":"182","author":"Krummel","year":"1995","journal-title":"J. Exp. Med."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1084\/jem.181.5.1911","article-title":"NKR-P1A is a target-specific receptor that activates natural killer cell cytotoxicity","volume":"181","author":"Ryan","year":"1995","journal-title":"J. Exp. Med."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1002\/eji.1830270111","article-title":"The cytoplasmic domain of rat NKR-P1 receptor interacts with the N-terminal domain of p56 lck via cysteine residues","volume":"27","author":"Campbell","year":"1997","journal-title":"Eur. J. Immunol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"6803","DOI":"10.1038\/s41598-023-33987-2","article-title":"Expansion of mixed immune cells using CD3\/CD161 co-stimulation for the treatment of cancer","volume":"13","author":"Tsumura","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Le Bourhis, L., Dusseaux, M., Bohineust, A., Bessoles, S., Martin, E., Premel, V., Cor\u00e9, M., Sleurs, D., Serriari, N.-E., and Treiner, E. (2013). MAIT Cells Detect and Efficiently Lyse Bacterially-Infected Epithelial Cells. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003681"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"3562","DOI":"10.1172\/JCI125957","article-title":"CD161 contributes to prenatal immune suppression of IFN-\u03b3\u2013producing PLZF+ T cells","volume":"129","author":"Halkias","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"112557","DOI":"10.1016\/j.cellsig.2026.112557","article-title":"The CAMK protein family: Pivotal roles in calcium-dependent disease pathways and emerging therapeutic strategies","volume":"144","author":"Fu","year":"2026","journal-title":"Cell. Signal."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"117932","DOI":"10.1016\/j.bcp.2026.117932","article-title":"Deciphering the immunomodulatory code: How metal nanoadjuvants orchestrate intracellular immune signaling cascades","volume":"249","author":"Fang","year":"2026","journal-title":"Biochem. Pharmacol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/35036035","article-title":"The versatility and universality of calcium signalling","volume":"1","author":"Berridge","year":"2000","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1146\/annurev-physiol-052424-082740","article-title":"Calcium Regulation of Mitochondrial Metabolism","volume":"88","author":"Mannella","year":"2026","journal-title":"Annu. Rev. Physiol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1146\/annurev-immunol-020711-075005","article-title":"Controlling natural killer cell responses: Integration of signals for activation and inhibition","volume":"31","author":"Long","year":"2013","journal-title":"Annu. Rev. Immunol."},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Mangalmurti, A., Bonheur, A., and Lukens, J.R. (2026). Microglial ITAM & ITIM Signaling in Neurodegenerative Disease and Brain Aging. J. Mol. Biol., 169910.","DOI":"10.1016\/j.jmb.2026.169910"},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"K, L., and Sundararajan, V. (2026). Immunological and pathological roles of Siglecs: A molecular review. Front. Immunol., 17.","DOI":"10.3389\/fimmu.2026.1826359"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S1043-6618(03)00050-1","article-title":"Intracellular signal transduction pathways activated by ceramide and its metabolites","volume":"47","author":"Ruvolo","year":"2003","journal-title":"Pharmacol. Res."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"e70103","DOI":"10.1002\/cbin.70103","article-title":"The Role of Sphingomyelin Synthase 2 in Lipid Metabolism and Its Implications in Diseases","volume":"50","author":"Sun","year":"2026","journal-title":"Cell Biol. Int."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"12722","DOI":"10.1074\/jbc.274.18.12722","article-title":"A novel pathway for tumor necrosis factor-alpha and ceramide signaling involving sequential activation of tyrosine kinase, p21(ras), and phosphatidylinositol 3-kinase","volume":"274","author":"Hanna","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"5977","DOI":"10.4049\/jimmunol.167.10.5977","article-title":"Ceramide Regulates Lipopolysaccharide-Induced Phosphatidylinositol 3-Kinase and Akt Activity in Human Alveolar Macrophages","volume":"167","author":"Monick","year":"2001","journal-title":"J. Immunol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1084\/jem.181.6.2059","article-title":"CD28 signals through acidic sphingomyelinase","volume":"181","author":"Boucher","year":"1995","journal-title":"J. Exp. Med."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"5183","DOI":"10.4049\/jimmunol.162.9.5183","article-title":"Signaling pathways activated by leukocyte function-associated Ag-1-dependent costimulation","volume":"162","author":"Ni","year":"1999","journal-title":"J. Immunol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"3366","DOI":"10.4049\/jimmunol.1400346","article-title":"CD39 and CD161 Modulate Th17 Responses in Crohn\u2019s Disease","volume":"193","author":"Bai","year":"2014","journal-title":"J. Immunol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"e2963","DOI":"10.1038\/cddis.2017.360","article-title":"Acid sphingomyelinase mediates human CD4+ T-cell signaling: Potential roles in T-cell responses and diseases","volume":"8","author":"Bai","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"2955","DOI":"10.1002\/eji.200425327","article-title":"Mini-review: Transendothelial migration of leukocytes: Through the front door or around the side of the house?","volume":"34","author":"Engelhardt","year":"2004","journal-title":"Eur. J. Immunol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"jcs263862","DOI":"10.1242\/jcs.263862","article-title":"Leukocyte transendothelial migration hotspots at a glance","volume":"138","author":"Tebbens","year":"2025","journal-title":"J. Cell Sci."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s11658-025-00797-5","article-title":"Endothelial activation during the diapedesis of cancer cells: Between the kiss of death and therapeutic breakthrough","volume":"30","author":"Piwowarczyk","year":"2025","journal-title":"Cell. Mol. Biol. Lett."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"946509","DOI":"10.1155\/2015\/946509","article-title":"Crossing the Vascular Wall: Common and Unique Mechanisms Exploited by Different Leukocyte Subsets during Extravasation","volume":"2015","author":"Schnoor","year":"2015","journal-title":"Mediat. Inflamm."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0165-2478(97)00050-3","article-title":"NKRP1A molecule is involved in transendothelial migration of CD4+ human T lymphocytes","volume":"57","author":"Poggi","year":"1997","journal-title":"Immunol. Lett."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"4349","DOI":"10.4049\/jimmunol.162.7.4349","article-title":"IL-12-mediated NKRP1A up-regulation and consequent enhancement of endothelial transmigration of V delta 2+ TCR gamma delta+ T lymphocytes from healthy donors and multiple sclerosis patients","volume":"162","author":"Poggi","year":"1999","journal-title":"J. Immunol."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1001\/2013.jamaneurol.409","article-title":"Enriched CD161 high CCR6 + \u03b3\u03b4 T Cells in the Cerebrospinal Fluid of Patients with Multiple Sclerosis","volume":"70","author":"Schirmer","year":"2013","journal-title":"JAMA Neurol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1093\/brain\/awq354","article-title":"CD161(high)CD8+T cells bear pathogenetic potential in multiple sclerosis","volume":"134","author":"Annibali","year":"2011","journal-title":"Brain"},{"key":"ref_172","doi-asserted-by":"crossref","unstructured":"De Federicis, D., Bassani, C., Chiarelli, R.R., Montini, F., Giordano, A., Esposito, F., Riva, N., Quattrini, A., Martinelli, V., and Filippi, M. (2024). Circulating MAIT cells in multiple sclerosis and amyotrophic lateral sclerosis. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1436717"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s10067-017-3800-9","article-title":"CD147-mediated chemotaxis of CD4+CD161+ T cells may contribute to local inflammation in rheumatoid arthritis","volume":"37","author":"Lv","year":"2018","journal-title":"Clin. Rheumatol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"563713","DOI":"10.1155\/2015\/563713","article-title":"Percentages of CD4+CD161+ and CD4-CD8-CD161+ T cells in the synovial fluid are correlated with disease activity in rheumatoid arthritis","volume":"2015","author":"Miao","year":"2015","journal-title":"Mediat. Inflamm."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"2601","DOI":"10.1007\/s10067-026-08056-4","article-title":"CD161+ Treg as a potential biomarker for evaluating disease activity and treatment efficacy in rheumatoid arthritis","volume":"45","author":"Song","year":"2026","journal-title":"Clin. Rheumatol."},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Balog, J.\u00c1., Zvara, \u00c1., Bukovinszki, V., Pusk\u00e1s, L.G., Balog, A., and Szebeni, G.J. (2024). Comparative single-cell multiplex immunophenotyping of therapy-naive patients with rheumatoid arthritis, systemic sclerosis, and systemic lupus erythematosus shed light on disease-specific composition of the peripheral immune system. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1376933"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1158\/2159-8290.CD-20-1808","article-title":"Therapeutic Targeting of the Tumor Microenvironment","volume":"11","author":"Bejarano","year":"2021","journal-title":"Cancer Discov."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.ccell.2023.01.010","article-title":"Spatial profiling technologies illuminate the tumor microenvironment","volume":"41","author":"Elhanani","year":"2023","journal-title":"Cancer Cell"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/s41577-025-01229-3","article-title":"Microenvironmental regulation of solid tumour resistance to CAR T cell therapy","volume":"26","author":"Lamplugh","year":"2026","journal-title":"Nat. Rev. Immunol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1111\/imm.70096","article-title":"Regulatory T Cell Metabolism in Cancer","volume":"177","author":"Mortezaee","year":"2026","journal-title":"Immunology"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s13045-026-01801-x","article-title":"Cytokines and cancer-associated fibroblasts","volume":"19","author":"Hu","year":"2026","journal-title":"J. Hematol. Oncol."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1007\/s00262-007-0391-3","article-title":"V\u03b39V\u03b42 T cell-mediated recognition of human solid tumors. Potential for immunotherapy of hepatocellular and colorectal carcinomas","volume":"57","author":"Cabillic","year":"2008","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"e003685","DOI":"10.1136\/jitc-2021-003685","article-title":"Activated but impaired IFN-\u03b3 production of mucosal-associated invariant T cells in patients with hepatocellular carcinoma","volume":"9","author":"Huang","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_184","doi-asserted-by":"crossref","unstructured":"Lavoie, J.M., Baichoo, P., Chavez, E., Nappi, L., Khalaf, D., Kollmannsberger, C.K., Chi, K.N., Weng, A., Steidl, C., and Eigl, B.J. (2022). Comprehensive immune profiling of patients with advanced urothelial or renal cell carcinoma receiving immune checkpoint blockade. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.973402"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1158\/2326-6066.CIR-22-0121","article-title":"Tissue-Resident Memory T Cells in Pancreatic Ductal Adenocarcinoma Coexpress PD-1 and TIGIT and Functional Inhibition Is Reversible by Dual Antibody Blockade","volume":"11","author":"Pearce","year":"2023","journal-title":"Cancer Immunol. Res."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"e014903","DOI":"10.1136\/jitc-2026-014903","article-title":"Clinical significance of CD161+CD8+ T cells in the tumor microenvironment of esophageal squamous cell carcinoma and their association with the 4-1BB signaling pathway","volume":"14","author":"Chen","year":"2026","journal-title":"J. Immunother. Cancer"},{"key":"ref_187","doi-asserted-by":"crossref","unstructured":"Li, H., Zhou, K., Wang, K., Cao, H., Wu, W., Wang, Z., Dai, Z., Chen, S., Peng, Y., and Xiao, G. (2022). A pan-cancer and single-cell sequencing analysis of CD161, a promising onco-immunological biomarker in tumor microenvironment and immunotherapy. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1040289"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"2815","DOI":"10.1182\/blood-2023-190957","article-title":"Anti-CD161 antibody IMT-009 is a novel immunotherapeutic agent that effectively blocks the inhibitory CLEC2D\/CD161 axis in CLEC2D+ B cell hematological malignancies reinvigorating T and NK cell function leading to anti-tumor benefit","volume":"142","author":"Bernstein","year":"2023","journal-title":"Blood"},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s00262-025-04251-5","article-title":"Comparative efficacy of combination regimens based on interventional therapy and immune checkpoint inhibitors (ICIs) in patients with intermediate- and advanced-stage hepatocellular carcinoma: A systematic review, meta-analysis, and network meta-analysis","volume":"75","author":"Su","year":"2026","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"218145","DOI":"10.1016\/j.canlet.2025.218145","article-title":"Current advances and future directions of combined ICIs and TILs in solid tumors","volume":"636","author":"Wang","year":"2026","journal-title":"Cancer Lett."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s11302-015-9457-4","article-title":"Beyond ecto-nucleotidase: CD39 defines human Th17 cells with CD161","volume":"11","author":"Bai","year":"2015","journal-title":"Purinergic Signal"},{"key":"ref_192","doi-asserted-by":"crossref","unstructured":"Tong, B., Wang, M., Liu, L., and Yang, X. (2025). Immunobiology roles of the human CD161 receptor in T cells. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1648305"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.smim.2013.10.011","article-title":"Reasons for rarity of Th17 cells in inflammatory sites of human disorders","volume":"25","author":"Annunziato","year":"2013","journal-title":"Semin. Immunol."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/9\/1302\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:01:02Z","timestamp":1788948062000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/9\/1302"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,9]]},"references-count":193,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["biom16091302"],"URL":"https:\/\/doi.org\/10.3390\/biom16091302","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,9]]}}}