{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:59:24Z","timestamp":1790834364222,"version":"4.1.0"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T00:00:00Z","timestamp":1636329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010124","name":"Erich und Gertrud Roggenbuck-Stiftung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010124","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005973","name":"Dr. Mildred Scheel Stiftung f\ufffdr Krebsforschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005973","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> \u03b3\u03b4 T cells represent a unique T cell subpopulation due to their ability to recognize cancer cells in a T cell receptor- (TCR) dependent manner, but also in a non-major histocompatibility complex- (MHC) restricted way via natural killer receptors (NKRs). Endowed with these features, they represent attractive effectors for immuno-therapeutic strategies with a better safety profile and a more favorable anti-tumor efficacy in comparison to conventional \u03b1\u03b2 T cells. Also, remarkable progress has been achieved re-activating exhausted T lymphocytes with inhibitors of co-regulatory receptors e.g., programmed cell death protein 1 (PD-1), T cell immunoreceptor with Ig and ITIM domains (TIGIT) and of the adenosine pathway (CD39, CD73). Regarding \u03b3\u03b4 T cells, little evidence is available. This study aimed to immunophenotypically characterize \u03b3\u03b4 T cells from patients with diagnosed acute myeloid leukemia (AML) in comparison to patients with multiple myeloma (MM) and healthy donors (HD).<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> The frequency, differentiation, activation, and exhaustion status of bone marrow- (BM) derived \u03b3\u03b4 T cells from patients with AML (<jats:italic>n<\/jats:italic> = 10) and MM (<jats:italic>n<\/jats:italic> = 11) were assessed in comparison to corresponding CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells and peripheral blood- (PB) derived \u03b3\u03b4 T cells from HDs (<jats:italic>n<\/jats:italic> = 16) using multiparameter flow cytometry.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> BM-infiltrating V\u03b41 T cells showed an increased terminally differentiated cell population (TEMRAs) in AML and MM in comparison to HDs with an aberrant subpopulation of CD27<jats:sup>\u2212<\/jats:sup>CD45RA<jats:sup>++<\/jats:sup> cells. TIGIT, PD-1, TIM-3, and CD39 were more frequently expressed by \u03b3\u03b4 T cells in comparison to the corresponding CD4<jats:sup>+<\/jats:sup> T cell population, with expression levels that were similar to that on CD8<jats:sup>+<\/jats:sup> effector cells in both hematologic malignancies. In comparison to V\u03b42 T cells, the increased frequency of PD-1<jats:sup>+<\/jats:sup>-, TIGIT<jats:sup>+<\/jats:sup>-, TIM-3<jats:sup>+<\/jats:sup>, and CD39<jats:sup>+<\/jats:sup> cells was specifically observed on V\u03b41 T cells and related to the TEMRA V\u03b41 population with a significant co-expression of PD-1 and TIM-3 together with TIGIT.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Our results revealed that BM-resident \u03b3\u03b4 T cells in AML and MM express TIGIT, PD-1, TIM-3 and CD39. As effector population for autologous and allogeneic strategies, inhibition of co-inhibitory receptors on especially V\u03b41 \u03b3\u03b4 T cells may lead to re-invigoration that could further increase their cytotoxic potential.<\/jats:p>","DOI":"10.3389\/fmed.2021.763773","type":"journal-article","created":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T05:38:41Z","timestamp":1636349921000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":40,"title":["Bone Marrow-Resident V\u03b41 T Cells Co-express TIGIT With PD-1, TIM-3 or CD39 in AML and Myeloma"],"prefix":"10.3389","volume":"8","author":[{"given":"Franziska","family":"Brauneck","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Weimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Schulze zur Wiesch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Weisel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Leypoldt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabi","family":"Vohwinkel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta","family":"Fritzsche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Bokemeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin","family":"Wellbrock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter","family":"Fiedler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"984","DOI":"10.3389\/fimmu.2018.00984","article-title":"Human \u03b3\u03b4 T-cells: from surface receptors to the therapy of high-risk leukemias","volume":"9","author":"Pistoia","year":"2018","journal-title":"Front. Immunol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"e1146843","DOI":"10.1080\/2162402X.2016.1146843","article-title":"BTN3A molecules considerably improve V\u03b39V\u03b42T cells-based immunotherapy in acute myeloid leukemia","volume":"5","author":"Benyamine","year":"2016","journal-title":"Oncoimmunology."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1614","DOI":"10.4161\/onci.21512","article-title":"Immunotherapy of acute myeloid leukemia based on\u03b3\u03bbd T cells","volume":"1","author":"Gertner-Dardenne","year":"2012","journal-title":"Oncoimmunology."},{"key":"B4","doi-asserted-by":"publisher","first-page":"2","DOI":"10.4161\/onci.23304","article-title":"Human v\u03b42 versus non-v\u03b42 \u03b3\u03b4 t cells in antitumor immunity","volume":"2","author":"Kabelitz","year":"2013","journal-title":"Oncoimmunology."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2636","DOI":"10.3389\/fimmu.2018.02636","article-title":"Tissue adaptations of memory and tissue-resident gamma delta T cells","volume":"9","author":"Khairallah","year":"2018","journal-title":"Front Immunol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"4701","DOI":"10.4049\/jimmunol.1103710","article-title":"Human V\u03b39V\u03b42 T cells specifically recognize and kill acute myeloid leukemic blasts","volume":"188","author":"Gertner-Dardenne","year":"2012","journal-title":"J Immunol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"575","DOI":"10.3389\/fimmu.2014.00575","article-title":"\u03b3\u03b4 T lymphocytes as a first line of immune defense: old and new ways of antigen recognition and implications for cancer immunotherapy","volume":"5","author":"Poggi","year":"2014","journal-title":"Front Immunol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.1084\/jem.20021515","article-title":"CD1-mediated \u03b3\/\u03b4 T cell maturation of dendritic cells","volume":"196","author":"Leslie","year":"2002","journal-title":"J Exp Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1006\/clim.2002.5218","article-title":"Human gamma delta T cells induce dendritic cell maturation","volume":"103","author":"Ismaili","year":"2002","journal-title":"Clin Immunol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1708","DOI":"10.4049\/jimmunol.1102654","article-title":"Human \u03b3\u03b4 T lymphocytes are licensed for professional antigen presentation by interaction with opsonized target cells","volume":"188","author":"Himoudi","year":"2012","journal-title":"J Immunol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1007\/s00262-015-1700-x","article-title":"Myeloid molecular characteristics of human \u03b3\u03b4 T cells support their acquisition of tumor antigen-presenting capacity","volume":"64","author":"Muto","year":"2015","journal-title":"Cancer Immunol Immunother."},{"key":"B12","doi-asserted-by":"publisher","first-page":"761","DOI":"10.3389\/fimmu.2017.00761","article-title":"Key features of gamma-delta T-cell subsets in human diseases and their immunotherapeutic implications","volume":"8","author":"Lawand","year":"2017","journal-title":"Front Immunol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1007\/s00262-007-0279-2","article-title":"Chemotherapy and zoledronate sensitize solid tumour cells to V\u03b39V\u03b42 T cell cytotoxicity","volume":"56","author":"Mattarollo","year":"2007","journal-title":"Cancer Immunol Immunother."},{"key":"B14","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1038\/nature14282","article-title":"IL-17-producing \u03b3\u03b4 T cells and neutrophils conspire to promote breast cancer metastasis","volume":"522","author":"Coffelt","year":"2015","journal-title":"Nature."},{"key":"B15","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1038\/s12276-021-00576-0","article-title":"Function of \u03b3\u03b4 T cells in tumor immunology and their application to cancer therapy","volume":"53","author":"Park","year":"2021","journal-title":"Exp Mol Med."},{"key":"B16","doi-asserted-by":"publisher","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":"B17","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1097\/CJI.0b013e318245bb1e","article-title":"Tumor-promoting versus tumor-antagonizing roles of \u03b3\u03b4 T cells in cancer immunotherapy: results from a prospective phase I\/II trial","volume":"35","author":"Kunzmann","year":"2012","journal-title":"J Immunother."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1479-5876-12-45","article-title":"Successful adoptive transfer and in vivo expansion of haploidentical \u03b3\u03b4 T cells","volume":"12","author":"Wilhelm","year":"2014","journal-title":"J Transl Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2349","DOI":"10.1182\/blood-2014-09-599423","article-title":"\u03b3\u03b4 T-cell reconstitution after HLA-haploidentical hematopoietic transplantation depleted of TCR-\u03b1\u03b2+\/CD19+ lymphocytes","volume":"125","author":"Airoldi","year":"2015","journal-title":"Blood."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1492","DOI":"10.3389\/fimmu.2018.01492","article-title":"V\u03b39V\u03b42 T cells in the bone marrow of myeloma patients: a paradigm of microenvironment-induced immune suppression","volume":"9","author":"Castella","year":"2018","journal-title":"Front Immunol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4110\/in.2020.20.e5","article-title":"Heterogeneity of human \u03b3\u03b4 t cells and their role in cancer immunity","volume":"20","author":"Lee","year":"2020","journal-title":"Immune Netw."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1395","DOI":"10.3389\/fimmu.2018.01395","article-title":"\u03b3\u03b4 T cells and tumor microenvironment: from immunosurveillance to tumor evasion","volume":"9","author":"Presti","year":"2018","journal-title":"Front Immunol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1038\/sj.bmt.1705650","article-title":"Long term disease-free survival in acute leukemia patients recovering with increased \u03b3\u03b4 T cells after partially mismatched related donor bone marrow transplantation","volume":"39","author":"Godder","year":"2007","journal-title":"Bone Marrow Transplant."},{"key":"B24","doi-asserted-by":"publisher","first-page":"e49878","DOI":"10.1371\/journal.pone.0049878","article-title":"Characterization of human \u03b3\u03b4 T lymphocytes infiltrating primary malignant melanomas","volume":"7","author":"Cordova","year":"2012","journal-title":"PLoS ONE."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.1038\/leu.2012.374","article-title":"\u03b3\u03b4T cells elicited by CMV reactivation after allo-SCT cross-recognize CMV and leukemia","volume":"27","author":"Scheper","year":"2013","journal-title":"Leukemia."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.3109\/14653249.2012.700766","article-title":"Human Vdelta1 gamma-delta T cells exert potent specific cytotoxicity against primary multiple myeloma cells","volume":"14","author":"Knight","year":"2012","journal-title":"Cytotherapy."},{"key":"B27","doi-asserted-by":"publisher","first-page":"e000957","DOI":"10.1136\/jitc-2020-000957","article-title":"TIGIT in cancer immunotherapy","volume":"8","author":"Chauvin","year":"2020","journal-title":"J Immunother Cancer."},{"key":"B28","doi-asserted-by":"publisher","first-page":"2046","DOI":"10.1172\/JCI80445","article-title":"TIGIT and PD-1 impair tumor antigen-specific CD8+ T cells in melanoma patients","volume":"125","author":"Chauvin","year":"2015","journal-title":"J Clin Invest."},{"key":"B29","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1016\/j.immuni.2016.05.001","article-title":"L1 Anderson AC, Joller, N. and Kuchroo VK. (2016) Lag-3, Tim-3, and TIGIT: co-inhibitory receptors with specialized functions in immune regulation. Immunity, NIH public access 44, 989\u20131004.ag-3, Tim-3, and TIGIT: co-inhibitory receptors with specia","volume":"44","author":"Anderson","year":"2016","journal-title":"Immunity."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/2162402X.2017.1364828","article-title":"PD-1 expression on tumor-specific T cells: friend or foe for immunotherapy?","volume":"7","author":"Simon","year":"2018","journal-title":"Oncoimmunology."},{"key":"B31","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1038\/s41577-019-0224-6","article-title":"TIM3 comes of age as an inhibitory receptor","volume":"20","author":"Wolf","year":"2020","journal-title":"Nat Rev Immunol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"3057","DOI":"10.1158\/1078-0432.CCR-15-2626","article-title":"T-cell immunoglobulin and ITIM domain (TIGIT) associates with CD8+ T-cell exhaustion and poor clinical outcome in AML patients","volume":"22","author":"Kong","year":"2016","journal-title":"Clin Cancer Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1111\/imr.12528","article-title":"The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets","volume":"276","author":"Allard","year":"2017","journal-title":"Immunol Rev."},{"key":"B34","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1038\/s41571-020-0382-2","article-title":"The adenosine pathway in immuno-oncology","volume":"17","author":"Allard","year":"2020","journal-title":"Nat Rev Clin Oncol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41586-019-1324-y","article-title":"TOX is a critical regulator of tumour-specific T cell differentiation","volume":"571","author":"Scott","year":"2019","journal-title":"Nature"},{"key":"B36","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/s41586-019-1325-x","article-title":"TOX transcriptionally and epigenetically programs CD8+ T cell exhaustion","volume":"571","author":"Khan","year":"2019","journal-title":"Nature."},{"key":"B37","doi-asserted-by":"publisher","first-page":"622509","DOI":"10.3389\/fimmu.2020.622509","article-title":"Exhausted CD8+T cells in the tumor immune microenvironment: new pathways to therapy","volume":"11","author":"Jiang","year":"2021","journal-title":"Front Immunol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2020\/4612952","article-title":"Characteristic of TIGIT and DNAM-1 Expression on Foxp3+ \u03b3\u03b4 T cells in AML patients","volume":"2020","author":"Jin","year":"2020","journal-title":"Biomed Res Int."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/2162402X.2016.1277305","article-title":"Tumor-infiltrating CD39+ \u03b3\u03b4Tregs are novel immunosuppressive T cells in human colorectal cancer","volume":"6","author":"Hu","year":"2017","journal-title":"Oncoimmunology."},{"key":"B40","doi-asserted-by":"publisher","first-page":"e1379642","DOI":"10.1080\/2162402X.2017.1379642","article-title":"IL-21 promotes the development of a CD73-positive V\u03b39V\u03b42 T cell regulatory population","volume":"7","author":"Barjon","year":"2018","journal-title":"Oncoimmunology."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.1016\/j.bbrc.2016.08.115","article-title":"CD27-CD45+ \u03b3\u03b4 T cells can be divided into two populations, CD27-CD45int and CD27-CD45hi with little proliferation potential","volume":"478","author":"Odaira","year":"2016","journal-title":"Biochem Biophys Res Commun."},{"key":"B42","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1038\/nri3862","article-title":"Molecular and cellular insights into T cell exhaustion","volume":"15","author":"Wherry","year":"2015","journal-title":"Nat Rev Immunol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1136\/jitc-2020-002274","article-title":"Dichotomous and stable gamma delta T-cell number and function in healthy individuals","volume":"9","author":"Ou","year":"2021","journal-title":"J Immunother Cancer."},{"key":"B44","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1038\/s41571-019-0297-y","article-title":"Engineering strategies to overcome the current roadblocks in CAR T cell therapy","volume":"17","author":"Rafiq","year":"2020","journal-title":"Nat Rev Clin Oncol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1172\/jci.insight.134939","article-title":"T cell optimization for graft-versusleukemia responses","volume":"5","author":"Biernacki","year":"2020","journal-title":"JCI Insight."},{"key":"B46","doi-asserted-by":"publisher","first-page":"618427","DOI":"10.3389\/fimmu.2020.618427","article-title":"Allogeneic CAR cell therapy\u2014more than a pipe dream","volume":"11","author":"Caldwell","year":"2021","journal-title":"Front Immunol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.3389\/fimmu.2020.01347","article-title":"Gamma-delta CAR-T cells show CAR-directed and independent activity against leukemia","volume":"11","author":"Rozenbaum","year":"2020","journal-title":"Front Immunol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.ymthe.2017.12.001","article-title":"Chimeric antigen receptor-engineered human gamma delta T cells: enhanced cytotoxicity with retention of cross presentation","volume":"26","author":"Capsomidis","year":"2018","journal-title":"Mol Ther."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1016\/j.ymthe.2017.03.002","article-title":"Avoidance of on-target off-tumor activation using a co-stimulation-only chimeric antigen receptor","volume":"25","author":"Fisher","year":"2017","journal-title":"Mol Ther."},{"key":"B50","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1038\/s41423-020-0504-x","article-title":"Cancer immunotherapy with \u03b3\u03b4 T cells: many paths ahead of us","volume":"17","author":"Kabelitz","year":"2020","journal-title":"Cell Mol Immunol."},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-021-01122-7","article-title":"Selective recruitment of \u03b3\u03b4 T cells by a bispecific antibody for the treatment of acute myeloid leukemia","author":"Ganesan","year":"2021","journal-title":"Leukemia."},{"key":"B52","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1111\/imr.12925","article-title":"Tumor resistance mechanisms and their consequences on \u03b3\u03b4 T cell activation","volume":"298","author":"Wesch","year":"2020","journal-title":"Immunol Rev."},{"key":"B53","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1046\/j.1365-2141.1998.00630.x","article-title":"Increase in V\u03b41+ \u03b3\u03b4 T cells in the peripheral blood and bone marrow as a selective feature of HIV-1 but not other virus infections","volume":"100","author":"Rossol","year":"1998","journal-title":"Br J Haematol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.clim.2004.08.017","article-title":"Characterization of NKR + T-cell subsets in human bone marrow: implications for immunosurveillance of neoplasia","volume":"114","author":"Dean","year":"2005","journal-title":"Clin Immunol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"1930391","DOI":"10.1080\/2162402X.2021.1930391","article-title":"Increased frequency of TIGIT CD73-CD8 T cells with a TOX TCF-1low profile in patients with newly diagnosed and relapsed AML","volume":"10","author":"Brauneck","year":"2021","journal-title":"Oncoimmunology."},{"key":"B56","doi-asserted-by":"publisher","first-page":"e1005661","DOI":"10.1371\/journal.ppat.1005661","article-title":"Exhaustion of activated CD8 T cells predicts disease progression in primary HIV-1 infection","volume":"12","author":"Hoffmann","year":"2016","journal-title":"PLoS Pathog."},{"key":"B57","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1158\/0008-5472.CAN-16-2684","article-title":"CD39 expression defines cell exhaustion in tumor-infiltrating CD8+ T cells","volume":"78","author":"Canale","year":"2018","journal-title":"Cancer Res."},{"key":"B58","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1080\/14737140.2021.1865814","article-title":"TIM-3 pathway dysregulation and targeting in cancer","volume":"21","author":"Zeidan","year":"2021","journal-title":"Expert Rev Anticancer Ther."},{"key":"B59","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1002\/eji.201040959","article-title":"Expression and function of PD-1 in human \u03b3\u03b4 T cells that recognize phosphoantigens","volume":"41","author":"Iwasaki","year":"2011","journal-title":"Eur J Immunol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.1016\/j.cell.2016.07.046","article-title":"\u03b3\u03b4 T cells support pancreatic oncogenesis by restraining \u03b1\u03b2 T cell activation","volume":"166","author":"Daley","year":"2016","journal-title":"Cell."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/2162402X.2018.1550618","article-title":"PD-1 signaling modulates interferon-\u03b3 production by Gamma Delta (\u03b3\u03b4) T-Cells in response to leukemia","volume":"8","author":"Hoeres","year":"2019","journal-title":"Oncoimmunology."},{"key":"B62","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1186\/s12916-017-0883-8","article-title":"Synergistic effect of IL-12 and IL-18 induces TIM3 regulation of \u03b3\u03b4 T cell function and decreases the risk of clinical malaria in children living in Papua New Guinea","volume":"15","author":"Schofield","year":"2017","journal-title":"BMC Med."},{"key":"B63","doi-asserted-by":"publisher","first-page":"111719","DOI":"10.1016\/j.yexcr.2019.111719","article-title":"Tim-3 suppresses the killing effect of V\u03b39V\u03b42 T cells on colon cancer cells by reducing perforin and granzyme B expression","volume":"386","author":"Li","year":"2020","journal-title":"Exp Cell Res."},{"key":"B64","doi-asserted-by":"publisher","first-page":"567472","DOI":"10.3389\/fimmu.2020.567472","article-title":"Decreased frequency of intestinal CD39+ \u03b3\u03b4+ T cells with tissue-resident memory phenotype in inflammatory bowel disease","volume":"11","author":"Libera","year":"2020","journal-title":"Front Immunol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"3574","DOI":"10.4049\/jimmunol.0901334","article-title":"Cutting edge: TGF-\u03b21 and IL-15 induce FOXP3 + \u03b3\u03b4 regulatory T cells in the presence of antigen stimulation","volume":"183","author":"Casetti","year":"2009","journal-title":"J Immunol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"311","DOI":"10.4049\/jimmunol.1800934","article-title":"\u03b3\u03b4 T Cell update: adaptate orchestrators of immune surveillance","volume":"203","author":"Hayday","year":"2019","journal-title":"J Immunol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1038\/cmi.2012.43","article-title":"\u03b3\u03b4-T cells: an unpolished sword in human anti-infection immunity","volume":"10","author":"Zheng","year":"2013","journal-title":"Cell Mol Immunol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/cti2.1080","article-title":"\u03b3\u03b4 T cells in cancer: a small population of lymphocytes with big implications","volume":"8","author":"Raverdeau","year":"2019","journal-title":"Clin Transl Immunol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1097\/CJI.0b013e31818955ad","article-title":"Immune response of human propagated gammadelta-T-cells to neuroblastoma recommend the Vdelta1+ subset for gammadelta-T-cell-based immunotherapy","volume":"31","author":"Schilbach","year":"2008","journal-title":"J Immunother."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2021.763773\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T05:38:47Z","timestamp":1636349927000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2021.763773\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,8]]},"references-count":69,"alternative-id":["10.3389\/fmed.2021.763773"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2021.763773","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,8]]},"article-number":"763773"}}