{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:38:12Z","timestamp":1791290292470,"version":"4.3.0"},"reference-count":73,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T00:00:00Z","timestamp":1676505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>CXCL13 is a potent chemoattractant cytokine that promotes the migration of cells expressing its cognate receptor, CXCR5. Accordingly, T follicular helper cells and B cells migrate towards B cell follicles in lymph nodes, where the resulting spatial proximity promotes B cell\/T cell interaction and antibody formation. Moreover, effector cells of the CXCL13\/CXCR5-associated immune axis express PD-1, with corresponding circulating cells occurring in the blood. The formation of so-called ectopic or tertiary lymphoid structures, recently detected in different cancer types, represents an integral part of this axis, particularly in the context of its emerging role in anti-tumor defense. These aspects of the CXCL13\/CXCR5-associated immune axis are highlighted in this review, which focuses on cutaneous malignant melanoma. Specifically, we elaborate on the role of this important immune axis as a possible ancillary target of immune checkpoint inhibition with anti-PD-1 antibodies in different therapeutic settings and as a potential source of predictive biomarkers regarding treatment efficacy.<\/jats:p>","DOI":"10.3390\/life13020553","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T02:52:56Z","timestamp":1676515976000},"page":"553","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Revisiting the Role of the CXCL13\/CXCR5-Associated Immune Axis in Melanoma: Potential Implications for Anti-PD-1-Related Biomarker Research"],"prefix":"10.3390","volume":"13","author":[{"given":"Magdalena","family":"Hoellwerth","sequence":"first","affiliation":[{"name":"Department of Dermatology and Allergology, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5897-2780","authenticated-orcid":false,"given":"Peter","family":"Koelblinger","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9750-0188","authenticated-orcid":false,"given":"Roland","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Harrer","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, Paracelsus Medical University, 5020 Salzburg, Austria"},{"name":"Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University and Center for Cognitive Neuroscience, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"472","DOI":"10.3322\/caac.21409","article-title":"Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual","volume":"67","author":"Gershenwald","year":"2017","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/S1470-2045(21)00065-6","article-title":"Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG\/KEYNOTE-054): Distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial","volume":"22","author":"Eggermont","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.1200\/JCO.2009.26.7609","article-title":"Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: Safety, clinical activity, pharmacodynamics, and immunologic correlates","volume":"28","author":"Brahmer","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1824","DOI":"10.1056\/NEJMoa1709030","article-title":"Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma","volume":"377","author":"Weber","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1016\/S1470-2045(22)00559-9","article-title":"Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma (KEYNOTE-716): Distant metastasis-free survival results of a multicentre, double-blind, randomised, phase 3 trial","volume":"23","author":"Long","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1056\/NEJMoa1504030","article-title":"Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma","volume":"373","author":"Larkin","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"8706","DOI":"10.18632\/oncotarget.24283","article-title":"Analysis of response rate with ANTI PD1\/PD-L1 monoclonal antibodies in advanced solid tumors: A meta-analysis of randomized clinical trials","volume":"9","author":"Lora","year":"2018","journal-title":"Oncotarget"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1056\/NEJMoa1802357","article-title":"Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma","volume":"378","author":"Eggermont","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1056\/NEJMoa1503093","article-title":"Pembrolizumab versus Ipilimumab in Advanced Melanoma","volume":"372","author":"Robert","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1038\/nrc1096","article-title":"Contribution of stem cells and differentiated cells to epidermal tumours","volume":"3","author":"Owens","year":"2003","journal-title":"Nat. Rev. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.ccell.2021.11.012","article-title":"Multiomic profiling of checkpoint inhibitor-treated melanoma: Identifying predictors of response and resistance, and markers of biological discordance","volume":"40","author":"Newell","year":"2022","journal-title":"Cancer Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1111\/bjd.18379","article-title":"Decline of programmed death-1-positive circulating T regulatory cells predicts more favourable clinical outcome of patients with melanoma under immune checkpoint blockade","volume":"182","author":"Gambichler","year":"2020","journal-title":"Br. J. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/nri2326","article-title":"Inhibitory B7-family molecules in the tumour microenvironment","volume":"8","author":"Zou","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/s41591-019-0357-y","article-title":"A single dose of neoadjuvant PD-1 blockade predicts clinical outcomes in resectable melanoma","volume":"25","author":"Huang","year":"2019","journal-title":"Nat. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e002157","DOI":"10.1136\/jitc-2020-002157","article-title":"Follicular helper-T cells restore CD8","volume":"9","author":"Niogret","year":"2021","journal-title":"J. Immunother. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1084\/jem.192.11.1553","article-title":"CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function","volume":"192","author":"Schaerli","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"401","DOI":"10.3389\/fimmu.2016.00401","article-title":"Understanding Immune Cells in Tertiary Lymphoid Organ Development: It Is All Starting to Come Together","volume":"7","author":"Jones","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1016\/j.immuni.2019.04.011","article-title":"T Follicular Helper Cell Biology: A Decade of Discovery and Diseases","volume":"50","author":"Crotty","year":"2019","journal-title":"Immunity"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.immuni.2010.12.012","article-title":"Human blood CXCR5(+)CD4(+) T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion","volume":"34","author":"Morita","year":"2011","journal-title":"Immunity"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1146\/annurev.immunol.23.021704.115628","article-title":"Chemokines, sphingosine-1-phosphate, and cell migration in secondary lymphoid organs","volume":"23","author":"Cyster","year":"2005","journal-title":"Annu. Rev. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1034\/j.1600-065X.2000.00618.x","article-title":"Follicular stromal cells and lymphocyte homing to follicles","volume":"176","author":"Cyster","year":"2000","journal-title":"Immunol. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2808","DOI":"10.1002\/1521-4141(200010)30:10<2808::AID-IMMU2808>3.0.CO;2-K","article-title":"A migratory population of skin-derived dendritic cells expresses CXCR5, responds to B lymphocyte chemoattractant in vitro, and co-localizes to B cell zones in lymph nodes in vivo","volume":"30","author":"Saeki","year":"2000","journal-title":"Eur. J. Immunol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1038\/ni.3054","article-title":"Pathophysiology of T follicular helper cells in humans and mice","volume":"16","author":"Ueno","year":"2015","journal-title":"Nat. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.immuni.2007.07.009","article-title":"Germinal-center organization and cellular dynamics","volume":"27","author":"Allen","year":"2007","journal-title":"Immunity"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.3389\/fimmu.2018.01884","article-title":"Insights Into the Molecular Mechanisms of T Follicular Helper-Mediated Immunity and Pathology","volume":"9","author":"Qin","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7867","DOI":"10.4049\/jimmunol.175.12.7867","article-title":"IL-21 induces differentiation of human naive and memory B cells into antibody-secreting plasma cells","volume":"175","author":"Ettinger","year":"2005","journal-title":"J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2702","DOI":"10.1073\/pnas.1520112113","article-title":"CXCL13 is a plasma biomarker of germinal center activity","volume":"113","author":"Lindqvist","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1038\/35876","article-title":"A B-cell-homing chemokine made in lymphoid follicles activates Burkitt\u2019s lymphoma receptor-1","volume":"391","author":"Gunn","year":"1998","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"188799","DOI":"10.1016\/j.bbcan.2022.188799","article-title":"CXCL13-CXCR5 axis: Regulation in inflammatory diseases and cancer","volume":"1877","author":"Wang","year":"2022","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1038\/nm.2425","article-title":"Foxp3+ follicular regulatory T cells control the germinal center response","volume":"17","author":"Linterman","year":"2011","journal-title":"Nat. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"850998","DOI":"10.3389\/fimmu.2022.850998","article-title":"Role of the CXCL13\/CXCR5 Axis in Autoimmune Diseases","volume":"13","author":"Pan","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/d41586-019-03943-0","article-title":"New predictors for immunotherapy responses sharpen our view of the tumour microenvironment","volume":"577","author":"Bruno","year":"2020","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1038\/nri2832","article-title":"New insights into the development of lymphoid tissues","volume":"10","author":"Mebius","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/0167-5699(95)80023-9","article-title":"High endothelial venules (HEVs): Specialized endothelium for lymphocyte migration","volume":"16","author":"Girard","year":"1995","journal-title":"Immunol. Today"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/s41568-019-0144-6","article-title":"Tertiary lymphoid structures in the era of cancer immunotherapy","volume":"19","author":"Petitprez","year":"2019","journal-title":"Nat. Rev. Cancer."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/ni1330","article-title":"Lymphoid organ development: From ontogeny to neogenesis","volume":"7","author":"Drayton","year":"2006","journal-title":"Nat. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1007\/s00109-010-0658-6","article-title":"The chemokine receptor CXCR5 is pivotal for ectopic mucosa-associated lymphoid tissue neogenesis in chronic Helicobacter pylori-induced inflammation","volume":"88","author":"Winter","year":"2010","journal-title":"J. Mol. Med. (Berl.)"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"969","DOI":"10.3390\/cancers6020969","article-title":"Role of Tertiary Lymphoid Structures (TLS) in Anti-Tumor Immunity: Potential Tumor-Induced Cytokines\/Chemokines that Regulate TLS Formation in Epithelial-Derived Cancers","volume":"6","author":"Pimenta","year":"2014","journal-title":"Cancers"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3997","DOI":"10.1158\/0008-5472.CAN-12-1377","article-title":"Neogenesis of lymphoid structures and antibody responses occur in human melanoma metastases","volume":"72","author":"Cipponi","year":"2012","journal-title":"Cancer Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.3389\/fimmu.2018.01707","article-title":"T Follicular Helper-Like Cells in Inflamed Non-Lymphoid Tissues","volume":"9","author":"Hutloff","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1002\/JLB.3MR0218-062R","article-title":"Role of chemokines in ectopic lymphoid structures formation in autoimmunity and cancer","volume":"104","author":"Nerviani","year":"2018","journal-title":"J. Leukoc. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e91487","DOI":"10.1172\/jci.insight.91487","article-title":"CXCL13-producing TFH cells link immune suppression and adaptive memory in human breast cancer","volume":"2","author":"Migliori","year":"2017","journal-title":"JCI Insight"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"836","DOI":"10.3892\/ol.2021.13097","article-title":"Tertiary lymphoid structure and B-cell-related pathways: A potential target in tumor immunotherapy","volume":"22","author":"Qin","year":"2021","journal-title":"Oncol. Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1038\/s41577-022-00693-5","article-title":"The link between circulating follicular helper T cells and autoimmunity","volume":"22","author":"Walker","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5191","DOI":"10.1172\/JCI76861","article-title":"Circulating T follicular regulatory and helper cells have memory-like properties","volume":"124","author":"Sage","year":"2014","journal-title":"J. Clin. Investig."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"176ra32","DOI":"10.1126\/scitranslmed.3005191","article-title":"Induction of ICOS+CXCR3+CXCR5+ TH cells correlates with antibody responses to influenza vaccination","volume":"5","author":"Bentebibel","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/nature12477","article-title":"Signatures of mutational processes in human cancer","volume":"500","author":"Alexandrov","year":"2013","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/nature12634","article-title":"Mutational landscape and significance across 12 major cancer types","volume":"502","author":"Kandoth","year":"2013","journal-title":"Nature"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"689076","DOI":"10.3389\/fimmu.2021.689076","article-title":"Prognostic Value of Neoantigen Load in Immune Checkpoint Inhibitor Therapy for Cancer","volume":"12","author":"Zou","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1002\/cncr.21283","article-title":"The predictive value of CD8, CD4, CD68, and human leukocyte antigen-D-related cells in the prognosis of cutaneous malignant melanoma with vertical growth phase","volume":"104","author":"Piras","year":"2005","journal-title":"Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.3389\/fimmu.2020.02105","article-title":"Tumor-Infiltrating Lymphocytes and Their Prognostic Value in Cutaneous Melanoma","volume":"11","author":"Maibach","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1126\/science.aad0095","article-title":"Genomic correlates of response to CTLA-4 blockade in metastatic melanoma","volume":"350","author":"Miao","year":"2015","journal-title":"Science"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"106132","DOI":"10.18632\/oncotarget.22190","article-title":"Immune system and melanoma biology: A balance between immunosurveillance and immune escape","volume":"8","author":"Passarelli","year":"2017","journal-title":"Oncotarget"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1056\/NEJMoa050092","article-title":"Distinct sets of genetic alterations in melanoma","volume":"353","author":"Curtin","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1034764","DOI":"10.3389\/fmed.2022.1034764","article-title":"CXCR5+CD8 T cells: Potential immunotherapy targets or drivers of immune-mediated adverse events?","volume":"9","author":"Turner","year":"2022","journal-title":"Front. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"101480","DOI":"10.1016\/j.smim.2021.101480","article-title":"Emerging concepts in PD-1 checkpoint biology","volume":"52","author":"Pauken","year":"2021","journal-title":"Semin. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/s41568-019-0235-4","article-title":"CD8+ T cell states in human cancer: Insights from single-cell analysis","volume":"20","author":"Thommen","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1038\/srep00765","article-title":"12-Chemokine gene signature identifies lymph node-like structures in melanoma: Potential for patient selection for immunotherapy?","volume":"2","author":"Messina","year":"2012","journal-title":"Sci. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"eabc4220","DOI":"10.1126\/scitranslmed.abc4220","article-title":"ARID1A mutation plus CXCL13 expression act as combinatorial biomarkers to predict responses to immune checkpoint therapy in mUCC","volume":"12","author":"Goswami","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"6125","DOI":"10.1158\/1078-0432.CCR-18-1481","article-title":"Prognostic Significance of Tumor-Infiltrating B Cells and Plasma Cells in Human Cancer","volume":"24","author":"Wouters","year":"2018","journal-title":"Clin Cancer Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"675146","DOI":"10.3389\/fimmu.2021.675146","article-title":"A Standardized Analysis of Tertiary Lymphoid Structures in Human Melanoma: Disease Progression- and Tumor Site-Associated Changes With Germinal Center Alteration","volume":"12","author":"Werner","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2873","DOI":"10.1172\/JCI67428","article-title":"CD4\u207a follicular helper T cell infiltration predicts breast cancer survival","volume":"123","author":"Loi","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"eabk1692","DOI":"10.1126\/sciimmunol.abk1692","article-title":"Multiplexed imaging mass cytometry of the chemokine milieus in melanoma characterizes features of the response to immunotherapy","volume":"7","author":"Hoch","year":"2022","journal-title":"Sci. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1158\/0008-5472.1089.65.3","article-title":"Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity","volume":"65","author":"Hirano","year":"2005","journal-title":"Cancer Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4311","DOI":"10.1200\/JCO.2013.51.4802","article-title":"Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma","volume":"31","author":"Weber","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/nature22079","article-title":"T-cell invigoration to tumour burden ratio associated with anti-PD-1 response","volume":"545","author":"Huang","year":"2017","journal-title":"Nature"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"110331","DOI":"10.1016\/j.celrep.2022.110331","article-title":"PD-1 blockade therapy promotes infiltration of tumor-attacking exhausted T cell clonotypes","volume":"38","author":"Nagasaki","year":"2022","journal-title":"Cell Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nature19330","article-title":"Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy","volume":"537","author":"Im","year":"2016","journal-title":"Nature"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/s41586-022-05368-8","article-title":"Neoadjuvant relatlimab and nivolumab in resectable melanoma","volume":"611","author":"Amaria","year":"2022","journal-title":"Nature"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/s41591-020-01211-7","article-title":"Survival and biomarker analyses from the OpACIN-neo and OpACIN neoadjuvant immunotherapy trials in stage III melanoma","volume":"27","author":"Rozeman","year":"2021","journal-title":"Nat. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.immuni.2018.03.023","article-title":"The Immune Landscape of Cancer","volume":"48","author":"Thorsson","year":"2018","journal-title":"Immunity"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1038\/s41590-022-01274-3","article-title":"PD-1 directed immunotherapy alters Tfh and humoral immune responses to seasonal influenza vaccine","volume":"23","author":"Herati","year":"2022","journal-title":"Nat Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/s41586-019-1922-8","article-title":"B cells and tertiary lymphoid structures promote immunotherapy response","volume":"577","author":"Helmink","year":"2020","journal-title":"Nature"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/2\/553\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:37:33Z","timestamp":1760121453000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/2\/553"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,16]]},"references-count":73,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["life13020553"],"URL":"https:\/\/doi.org\/10.3390\/life13020553","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,16]]}}}