{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:52:29Z","timestamp":1792601549207,"version":"4.5.0"},"reference-count":77,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    <jats:italic>PTPN6<\/jats:italic>\n                    encodes SHP-1, a central regulator of immune tolerance and a critical signaling brake across innate and adaptive immunity in autoimmune disease. Predominantly expressed in hematopoietic cells, SHP-1 restrains receptor-proximal signaling downstream of antigen, cytokine, and pattern-recognition receptors, thereby setting activation thresholds that preserve immune homeostasis and limit autoreactivity. Converging evidence from human genetics, patient-derived immune cells, and animal models indicates that diminished SHP-1 activity promotes persistent autoreactive lymphocyte responses, exaggerated inflammatory signaling, and tissue-specific injury across systemic lupus erythematosus, rheumatoid arthritis, neutrophilic dermatoses, multiple sclerosis, psoriasis, and type 1 diabetes. Beyond its role in disease pathogenesis, SHP-1 has emerged as a therapeutically relevant node, particularly through strategies designed to enhance phosphatase activity and restore immune restraint. However, clinical translation remains constrained by challenges in phosphatase selectivity, context-dependent biology, and tissue-specific delivery. This review integrates current understanding of SHP-1 regulatory mechanisms, disease-specific evidence, and emerging translational opportunities, highlighting\n                    <jats:italic>PTPN6<\/jats:italic>\n                    \/SHP-1 as a candidate target for precision immunomodulation in autoimmune disease.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1839744","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T05:45:37Z","timestamp":1779255937000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["PTPN6\/SHP-1 in autoimmune disease: immune tolerance, regulatory mechanisms, and therapeutic targeting"],"prefix":"10.3389","volume":"17","author":[{"given":"Rachel C.","family":"Chang","sequence":"first","affiliation":[{"name":"Department of Dermatology, Rush University Medical Center","place":["Chicago, IL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Lasalle","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Rush University Medical Center","place":["Chicago, IL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Rush University Medical Center","place":["Chicago, IL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrienn","family":"Markovics","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Rheumatology, Rush University Medical Center","place":["Chicago, IL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle T.","family":"Amber","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Rush University Medical Center","place":["Chicago, IL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian P.","family":"Mansini","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Rush University Medical Center","place":["Chicago, IL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12395","article-title":"Human autoimmune diseases: a comprehensive update","volume":"278","author":"Wang","year":"2015","journal-title":"J Intern Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2023.103359","article-title":"Temporal trends in the prevalence of autoimmune diseases from 1990 to 2019","volume":"22","author":"Cao","year":"2023","journal-title":"Autoimmun Rev"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-024-00994-x","article-title":"The regulation and differentiation of regulatory T cells and their dysfunction in autoimmune diseases","volume":"24","author":"Sumida","year":"2024","journal-title":"Nat Rev Immunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.jaci.2015.10.023","article-title":"Alterations in immune function with biologic therapies for autoimmune disease","volume":"137","author":"Her","year":"2016","journal-title":"J Allergy Clin Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-022-00618-w","article-title":"Targeting protein phosphatases in cancer immunotherapy and autoimmune disorders","volume":"22","author":"Stanford","year":"2023","journal-title":"Nat Rev Drug Discov"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.2mr0317-105r","article-title":"Shp1 function in myeloid cells","volume":"102","author":"Abram","year":"2017","journal-title":"J Leukoc Biol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.immuni.2007.04.016","article-title":"B cell-specific deletion of protein-tyrosine phosphatase Shp1 promotes B-1a cell development and causes systemic autoimmunity","volume":"27","author":"Pao","year":"2007","journal-title":"Immunity"},{"key":"B8","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1186\/s13075-020-02250-8","article-title":"Regulation of autoimmune arthritis by the SHP-1 tyrosine phosphatase","volume":"22","author":"Markovics","year":"2020","journal-title":"Arthritis Res Ther"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m210430200","article-title":"Crystal structure of human protein-tyrosine phosphatase SHP-1*","volume":"278","author":"Yang","year":"2003","journal-title":"J Biol Chem"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.7554\/elife.74276","article-title":"Molecular features underlying differential SHP1\/SHP2 binding of immune checkpoint receptors","volume":"10","author":"Xu","year":"2021","journal-title":"eLife"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065x.2008.00760.x","article-title":"SHP-1 and SHP-2 in T cells: two phosphatases functioning at many levels","volume":"228","author":"Lorenz","year":"2009","journal-title":"Immunol Rev"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.2.945","article-title":"SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation","volume":"173","author":"Chemnitz","year":"2004","journal-title":"J Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2012.03.003","article-title":"Increased promoter methylation of the immune regulatory gene SHP-1 in leukocytes of multiple sclerosis subjects","volume":"246","author":"Kumagai","year":"2012","journal-title":"J Neuroimmunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001675","article-title":"The phosphatase SRC homology region 2 domain-containing phosphatase-1 is an intrinsic central regulator of dendritic cell function","volume":"186","author":"Ramachandran","year":"2011","journal-title":"J Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1103210","article-title":"Dendritic cell-specific ablation of the protein tyrosine phosphatase Shp1 promotes Th1 cell differentiation and induces autoimmunity","volume":"188","author":"Kaneko","year":"2012","journal-title":"J Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/ni0311-271e","article-title":"Phosphatase SHP-1 promotes TLR- and RIG-I-activated production of type I interferon by inhibiting the kinase IRAK1","volume":"9","author":"An","year":"2008","journal-title":"Nat Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v100.5.1852.h81702001852_1852_1859","article-title":"SHP-1 regulates Fcgamma receptor-mediated phagocytosis and the activation of RAC","volume":"100","author":"Kant","year":"2002","journal-title":"Blood"},{"key":"B18","doi-asserted-by":"publisher","first-page":"54","DOI":"10.4049\/jimmunol.202.supp.59.4","article-title":"Ptpn6 inhibits caspase-8- and Ripk3\/Mlkl-dependent inflammation","volume":"21","author":"Speir","year":"2020","journal-title":"Nat Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108468","article-title":"SHP-1 regulates antigen cross-presentation and is exploited by leishmania to evade immunity","volume":"33","author":"Khouili","year":"2020","journal-title":"Cell Rep"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.09.034","article-title":"M. tuberculosis-initiated human mannose receptor signaling regulates macrophage recognition and vesicle trafficking by fcR\u03b3-chain, grb2, and SHP-1","volume":"21","author":"Rajaram","year":"2017","journal-title":"Cell Rep"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.64898\/2026.01.21.699761","article-title":"Reduced late endosome\/lysosome function promotes SLE through chronic PI3K activity and SHP-1\/SHIP-1 defects","volume":"11","author":"Kang","year":"2026","journal-title":"JCI Insight"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ade3942","article-title":"CD47 halts Ptpn6-deficient neutrophils from provoking lethal inflammation","volume":"9","author":"Mazgaeen","year":"2023","journal-title":"Sci Adv"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1172\/jci183161","article-title":"Neutrophil-specific Shp1 loss results in lethal pulmonary hemorrhage in mouse models of acute lung injury","volume":"134","author":"Moussavi-Harami","year":"2024","journal-title":"J Clin Invest"},{"key":"B24","doi-asserted-by":"publisher","first-page":"397","DOI":"10.4049\/jimmunol.2300462","article-title":"SHP-1 regulates CD8+ T cell effector function but plays a subtle role with SHP-2 in T cell exhaustion due to a stage-specific nonredundant functional relay","volume":"212","author":"Hou","year":"2024","journal-title":"J Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.2133oia94","article-title":"Continuous inhibitory signaling by both SHP-1 and SHIP-1 pathways is required to maintain unresponsiveness of anergic B cells","volume":"213","author":"Getahun","year":"2016","journal-title":"J Exp Med"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1999","DOI":"10.1093\/intimm\/11.12.1999","article-title":"The tyrosine phosphatase SHP-1 influences thymocyte selection by setting TCR signaling thresholds","volume":"11","author":"Carter","year":"1999","journal-title":"Int Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20122239","article-title":"Shp1 regulates T cell homeostasis by limiting IL-4 signals","volume":"210","author":"Johnson","year":"2013","journal-title":"J Exp Med"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.162.11.6359","article-title":"The Src-homology domain 2-bearing protein tyrosine phosphatase-1 inhibits antigen receptor-induced apoptosis of activated peripheral T cells","volume":"162","author":"Zhang","year":"1999","journal-title":"J Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01658-z","article-title":"Harnessing CD3 diversity to optimize CAR T cells","volume":"24","author":"Velasco C\u00e1rdenas","year":"2023","journal-title":"Nat Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000622","article-title":"The protein tyrosine phosphatase SHP-1 modulates the suppressive activity of regulatory T cells","volume":"185","author":"Iype","year":"2010","journal-title":"J Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1602171","article-title":"T cells deficient in the tyrosine phosphatase SHP-1 resist suppression by regulatory T cells","volume":"199","author":"Mercadante","year":"2017","journal-title":"J Immunol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1139326","article-title":"Treg-specific deletion of the phosphatase SHP-1 impairs control of inflammation in vivo","volume":"14","author":"Gu","year":"2023","journal-title":"Front Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001362","article-title":"SHP-1 in T cells limits the production of CD8 effector cells without impacting the formation of long-lived central memory cells","volume":"185","author":"Fowler","year":"2010","journal-title":"J Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.cir-19-0690","article-title":"Inhibition of SHP-1 expands the repertoire of antitumor T cells available to respond to immune checkpoint blockade","volume":"8","author":"Snook","year":"2020","journal-title":"Cancer Immunol Res"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1042\/bst20150251","article-title":"SHP-1: the next checkpoint target for cancer immunotherapy","volume":"44","author":"Watson","year":"2016","journal-title":"Biochem Soc Trans"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1101\/2025.01.03.631277","article-title":"T lymphocyte-specific deletion of SHP1 and SHP2 promotes activation-induced cell death of CD4+ T cells and impairs antitumor response","volume":"122","author":"Foster","year":"2025","journal-title":"Proc Natl Acad Sci"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf1292","article-title":"T cell costimulatory receptor CD28 is a primary target for PD-1-mediated inhibition","volume":"355","author":"Hui","year":"2017","journal-title":"Science"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-024-01847-4","article-title":"The BTLA-HVEM axis restricts CAR T cell efficacy in cancer","volume":"25","author":"Guruprasad","year":"2024","journal-title":"Nat Immunol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-010879","article-title":"Shp-1 regulates the activity of low-affinity T cells specific to endogenous self-antigen during melanoma tumor growth and drives resistance to immune checkpoint inhibition","volume":"13","author":"Matous","year":"2025","journal-title":"J Immunother Cancer"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3109\/08916930109008048","article-title":"Expression of B cell receptor-associated signaling molecules in human lupus","volume":"33","author":"Huck","year":"2001","journal-title":"Autoimmunity"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2022.108952","article-title":"Dysregulated protein kinase\/phosphatase networks in SLE T cells","volume":"236","author":"Su\u00e1rez-Rojas","year":"2022","journal-title":"Clin Immunol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1172\/jci87037","article-title":"Inhibition of SHP2 ameliorates the pathogenesis of systemic lupus erythematosus","volume":"126","author":"Wang","year":"2016","journal-title":"J Clin Invest"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2010.12.035","article-title":"Alteration in the gene encoding protein tyrosine phosphatase nonreceptor type 6 (PTPN6\/SHP1) may contribute to neutrophilic dermatoses","volume":"178","author":"Nesterovitch","year":"2011","journal-title":"Am J Pathol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2010.12.053","article-title":"Spontaneous insertion of a b2 element in the ptpn6 gene drives a systemic autoinflammatory disease in mice resembling neutrophilic dermatosis in humans","volume":"178","author":"Nesterovitch","year":"2011","journal-title":"Am J Pathol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1186\/ar2618","article-title":"In vitro model for the analysis of synovial fibroblast-mediated degradation of intact cartilage","volume":"11","author":"Pretzel","year":"2009","journal-title":"Arthritis Res Ther"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901784","article-title":"ERK-dependent T cell receptor threshold calibration in rheumatoid arthritis","volume":"183","author":"Singh","year":"2009","journal-title":"J Immunol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2009.32","article-title":"Macrophages of multiple sclerosis patients display deficient SHP-1 expression and enhanced inflammatory phenotype","volume":"89","author":"Christophi","year":"2009","journal-title":"Lab Invest"},{"key":"B48","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1002\/glia.1096","article-title":"Upregulation of transcription factors controlling MHC expression in multiple sclerosis lesions","volume":"36","author":"Gobin","year":"2001","journal-title":"Glia"},{"key":"B49","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.clim.2009.05.019","article-title":"Interferon-beta treatment in multiple sclerosis attenuates inflammatory gene expression through inducible activity of the phosphatase SHP-1","volume":"133","author":"Christophi","year":"2009","journal-title":"Clin Immunol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01210-08","article-title":"Modulation of macrophage infiltration and inflammatory activity by the phosphatase SHP-1 in virus-induced demyelinating disease","volume":"83","author":"Christophi","year":"2009","journal-title":"J Virol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700720","article-title":"SHP-1 deficiency and increased inflammatory gene expression in PBMCs of multiple sclerosis patients","volume":"88","author":"Christophi","year":"2008","journal-title":"Lab Invest"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1530\/jme-17-0089","article-title":"Differential regulation of pro-inflammatory cytokine signalling by protein tyrosine phosphatases in pancreatic \u03b2-cells","volume":"59","author":"Stanley","year":"2017","journal-title":"J Mol Endocrinol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2010.6","article-title":"Deficient SOCS3 and SHP-1 expression in psoriatic T cells","volume":"130","author":"Eriksen","year":"2010","journal-title":"J Invest Dermatol"},{"key":"B54","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s42003-025-07629-4","article-title":"Single cell transcriptome profiling reveals pathogenesis of bullous pemphigoid","volume":"8","author":"Liang","year":"2025","journal-title":"Commun Biol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.6b00537","article-title":"Drugging the undruggable: Therapeutic potential of targeting protein tyrosine phosphatases","volume":"50","author":"Zhang","year":"2017","journal-title":"Acc Chem Res"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2017.03.004","article-title":"Targeting tyrosine phosphatases: Time to end the stigma","volume":"38","author":"Stanford","year":"2017","journal-title":"Trends Pharmacol Sci"},{"key":"B57","doi-asserted-by":"publisher","first-page":"279781","DOI":"10.1155\/2013\/279781","article-title":"The endothelial tyrosine phosphatase SHP-1 plays an important role for vascular haemostasis in TNF\u03b1 -induced inflammation in vivo","volume":"2013","author":"Koch","year":"2013","journal-title":"Mediators Inflammation"},{"key":"B58","doi-asserted-by":"publisher","first-page":"2218","DOI":"10.1038\/s41598-017-02512-7","article-title":"Hepatocyte SHP-1 is a critical modulator of inflammation during endotoxemia","volume":"7","author":"Adhikari","year":"2017","journal-title":"Sci Rep"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1038\/nature18621","article-title":"Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases","volume":"535","author":"Chen","year":"2016","journal-title":"Nature"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202525126","article-title":"Discovery of a first-in-class covalent allosteric SHP1 inhibitor with immunotherapeutic activity","volume":"65","author":"Qu","year":"2026","journal-title":"Angew Chem Int Ed Engl"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c00471","article-title":"Discovery of SHP2-D26 as a first, potent, and effective PROTAC degrader of SHP2 protein","volume":"63","author":"Wang","year":"2020","journal-title":"J Med Chem"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.25864","article-title":"Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity","volume":"129","author":"Wilhelm","year":"2011","journal-title":"Int J Cancer"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2017.114","article-title":"The tyrosine kinase inhibitor nintedanib activates SHP-1 and induces apoptosis in triple-negative breast cancer cells","volume":"49","author":"Liu","year":"2017","journal-title":"Exp Mol Med"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.155747","article-title":"Targeted activation of the SHP-1\/PP2A signaling axis elicits apoptosis of chronic lymphocytic leukemia cells","volume":"102","author":"Tibaldi","year":"2017","journal-title":"Haematologica"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0806619105","article-title":"Inflammation and autoimmunity caused by a SHP1 mutation depend on IL-1, MyD88, and a microbial trigger","volume":"105","author":"Croker","year":"2008","journal-title":"Proc Natl Acad Sci"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.03.014","article-title":"Tyrosine kinase SYK licenses MyD88 adaptor protein to instigate IL-1\u03b1-mediated inflammatory disease","volume":"46","author":"Gurung","year":"2017","journal-title":"Immunity"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-0343-4","article-title":"Immune checkpoint signaling and cancer immunotherapy","volume":"30","author":"He","year":"2020","journal-title":"Cell Res"},{"key":"B68","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.apsb.2020.07.010","article-title":"Tyrosine phosphatase SHP2 inhibitors in tumor-targeted therapies","volume":"11","author":"Song","year":"2021","journal-title":"Acta Pharm Sin B"},{"key":"B69","article-title":"SHP2 inhibitor BBP-398 in combination with nivolumab in patients with advanced non-small cell lung cancer with a KRAS mutation","volume-title":"U.S. National library of medicine, national institutes of health","year":"2026"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2023.04.002","article-title":"Immune mechanisms of toxicity from checkpoint inhibitors","volume":"9","author":"Wang","year":"2023","journal-title":"Trends Cancer"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1200552","article-title":"Abrogation of SRC homology region 2 domain-containing phosphatase 1 in tumor-specific T cells improves efficacy of adoptive immunotherapy by enhancing the effector function and accumulation of short-lived effector T cells in vivo","volume":"189","author":"Stromnes","year":"2012","journal-title":"J Immunol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20171477","article-title":"SHP-1 regulates hematopoietic stem cell quiescence by coordinating TGF-\u03b2 signaling","volume":"215","author":"Jiang","year":"2018","journal-title":"J Exp Med"},{"key":"B73","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1186\/s40164-023-00450-x","article-title":"CRISPR\/Cas9-mediated knockout of intracellular molecule SHP-1 enhances tumor-killing ability of CD133-targeted CAR T cells in vitro","volume":"12","author":"Liu","year":"2023","journal-title":"Exp Hematol Oncol"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2025.112266","article-title":"CRISPR\/Cas9-mediated SHP-1-knockout T cells combined with simvastatin enhances anti-tumor activity in humanized-PDX HCC model","volume":"28","author":"Liu","year":"2025","journal-title":"iScience"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.00294-16","article-title":"SHP-1 acts as a key regulator of alloresponses by modulating LFA-1-mediated adhesion in primary murine T cells","volume":"36","author":"Sauer","year":"2016","journal-title":"Mol Cell Biol"},{"key":"B76","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1186\/s12943-022-01559-z","article-title":"Engineering the next-generation of CAR T-cells with CRISPR-Cas9 gene editing","volume":"21","author":"Dimitri","year":"2022","journal-title":"Mol Cancer"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241512317","article-title":"CRISPR\/Cas9: A powerful strategy to improve CAR-T cell persistence","volume":"24","author":"Wei","year":"2023","journal-title":"Int J Mol Sci"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1839744\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T05:45:38Z","timestamp":1779255938000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1839744\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,20]]},"references-count":77,"alternative-id":["10.3389\/fimmu.2026.1839744"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1839744","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,20]]},"article-number":"1839744"}}