{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:04:15Z","timestamp":1790737455058,"version":"4.1.0"},"reference-count":75,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:00:00Z","timestamp":1738627200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:00:00Z","timestamp":1738627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82204805"],"award-info":[{"award-number":["82204805"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Project of the National Science Fund of Anhui Province","award":["2023AH050866"],"award-info":[{"award-number":["2023AH050866"]}]},{"name":"Outstanding Young Teacher Project of Colleges and Universities of Anhui Province","award":["YQYB2024030"],"award-info":[{"award-number":["YQYB2024030"]}]},{"name":"The Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine \u201cXinglin Talents\u201d cultivation plan project","award":["2023-0500-48-46"],"award-info":[{"award-number":["2023-0500-48-46"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Biol Proced Online"],"DOI":"10.1186\/s12575-025-00265-6","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T10:38:19Z","timestamp":1738665499000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Mechanisms of T-cell Depletion in Tumors and Advances in Clinical Research"],"prefix":"10.1186","volume":"27","author":[{"given":"Xiangfei","family":"Su","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuewei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,4]]},"reference":[{"key":"265_CR1","doi-asserted-by":"crossref","unstructured":"Choi Y, Shi Y, Haymaker CL, Naing A, Ciliberto G, Hajjar J. T-cell agonists in cancer immunotherapy. J Immunother Cancer 2020, 8(2).","DOI":"10.1136\/jitc-2020-000966"},{"issue":"6","key":"265_CR2","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1038\/s41422-022-00627-9","volume":"32","author":"J He","year":"2022","unstructured":"He J, Xiong X, Yang H, Li D, Liu X, Li S, Liao S, Chen S, Wen X, Yu K, et al. Defined tumor antigen-specific T cells potentiate personalized TCR-T cell therapy and prediction of immunotherapy response. Cell Res. 2022;32(6):530\u201342.","journal-title":"Cell Res"},{"key":"265_CR3","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.cyto.2017.10.001","volume":"104","author":"DM Shaw","year":"2018","unstructured":"Shaw DM, Merien F, Braakhuis A, Dulson D. T-cells and their cytokine production: the anti-inflammatory and immunosuppressive effects of strenuous exercise. Cytokine. 2018;104:136\u201342.","journal-title":"Cytokine"},{"issue":"4","key":"265_CR4","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1016\/j.immuni.2007.08.014","volume":"27","author":"X Cao","year":"2007","unstructured":"Cao X, Cai SF, Fehniger TA, Song J, Collins LI, Piwnica-Worms DR, Ley TJ. Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance. Immunity. 2007;27(4):635\u201346.","journal-title":"Immunity"},{"key":"265_CR5","doi-asserted-by":"crossref","unstructured":"Corrado M, Pearce EL. Targeting memory T cell metabolism to improve immunity. J Clin Investig. 2022;132(1).","DOI":"10.1172\/JCI148546"},{"key":"265_CR6","doi-asserted-by":"publisher","first-page":"874589","DOI":"10.3389\/fimmu.2022.874589","volume":"13","author":"Y Pu","year":"2022","unstructured":"Pu Y, Ji Q. Tumor-Associated macrophages regulate PD-1\/PD-L1 immunosuppression. Front Immunol. 2022;13:874589.","journal-title":"Front Immunol"},{"issue":"4","key":"265_CR7","first-page":"485","volume":"15","author":"F Kong","year":"2023","unstructured":"Kong F, Wang C, Zhang J, Wang X, Sun B, Xiao X, Zhang H, Song Y, Jia Y. Chinese herbal medicines for prostate cancer therapy: from experimental research to clinical practice. Chin Herb Med. 2023;15(4):485\u201395.","journal-title":"Chin Herb Med"},{"issue":"6","key":"265_CR8","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1158\/2326-6066.CIR-20-0989","volume":"9","author":"H Aoki","year":"2021","unstructured":"Aoki H, Ueha S, Shichino S, Ogiwara H, Shitara K, Shimomura M, Suzuki T, Nakatsura T, Yamashita M, Kitano S, et al. Transient depletion of CD4(+) cells induces remodeling of the TCR repertoire in gastrointestinal Cancer. Cancer Immunol Res. 2021;9(6):624\u201336.","journal-title":"Cancer Immunol Res"},{"issue":"4","key":"265_CR9","first-page":"509","volume":"15","author":"F Kong","year":"2023","unstructured":"Kong F, Wang C, Zhao L, Liao D, Wang X, Sun B, Yang P, Jia Y. Traditional Chinese medicines for non-small cell lung cancer: therapies and mechanisms. Chin Herb Med. 2023;15(4):509\u201315.","journal-title":"Chin Herb Med"},{"key":"265_CR10","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.cytogfr.2022.07.003","volume":"67","author":"J Lu","year":"2022","unstructured":"Lu J, Wu J, Mao L, Xu H, Wang S. Revisiting PD-1\/PD-L pathway in T and B cell response: beyond immunosuppression. Cytokine Growth Factor Rev. 2022;67:58\u201365.","journal-title":"Cytokine Growth Factor Rev"},{"issue":"7","key":"265_CR11","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1016\/j.ccell.2021.06.012","volume":"39","author":"GM Delgoffe","year":"2021","unstructured":"Delgoffe GM, Xu C, Mackall CL, Green MR, Gottschalk S, Speiser DE, Zehn D, Beavis PA. The role of exhaustion in CAR T cell therapy. Cancer Cell. 2021;39(7):885\u20138.","journal-title":"Cancer Cell"},{"issue":"1","key":"265_CR12","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1186\/s13045-021-01156-5","volume":"14","author":"JA Park","year":"2021","unstructured":"Park JA, Wang L, Cheung NV. Modulating tumor infiltrating myeloid cells to enhance bispecific antibody-driven T cell infiltration and anti-tumor response. J Hematol Oncol. 2021;14(1):142.","journal-title":"J Hematol Oncol"},{"issue":"8","key":"265_CR13","doi-asserted-by":"publisher","first-page":"44","DOI":"10.53388\/TMR20230210002","volume":"8","author":"PY Dong","year":"2023","unstructured":"Dong PY, Liang SL, Li L, Liu J, Zhang XF. Lotus root polysaccharide inhibits the growth of ovarian cancer cells by blocking the cell cycle. Tradit Med Res. 2023;8(8):44.","journal-title":"Tradit Med Res"},{"key":"265_CR14","doi-asserted-by":"crossref","unstructured":"Hong MMY, Maleki Vareki S. Addressing the Elephant in the immunotherapy room: Effector T-Cell Priming versus Depletion of Regulatory T-Cells by Anti-CTLA-4 therapy. Cancers. 2022;14(6).","DOI":"10.3390\/cancers14061580"},{"issue":"2","key":"265_CR15","first-page":"244","volume":"14","author":"W Zhang","year":"2022","unstructured":"Zhang W, Cui N, Ye J, Yang B, Sun Y, Kuang H. Curcumin\u2019s prevention of inflammation-driven early gastric cancer and its molecular mechanism. Chin Herb Med. 2022;14(2):244\u201353.","journal-title":"Chin Herb Med"},{"issue":"6230","key":"265_CR16","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1126\/science.aaa1348","volume":"348","author":"NA Rizvi","year":"2015","unstructured":"Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, Lee W, Yuan J, Wong P, Ho TS, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Sci (New York NY). 2015;348(6230):124\u20138.","journal-title":"Sci (New York NY)"},{"issue":"7528","key":"265_CR17","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1038\/nature13954","volume":"515","author":"PC Tumeh","year":"2014","unstructured":"Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515(7528):568\u201371.","journal-title":"Nature"},{"key":"265_CR18","first-page":"1160","volume-title":"Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade","author":"KE Pauken","year":"2016","unstructured":"Pauken KE, Sammons MA, Odorizzi PM, Manne S, Godec J, Khan O, Drake AM, Chen Z, Sen DR, Kurachi M, et al. Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade. Volume 354. New York, NY): Science; 2016. pp. 1160\u20135. 6316."},{"issue":"4","key":"265_CR19","first-page":"479","volume":"14","author":"Z Li","year":"2022","unstructured":"Li Z, Hao E, Cao R, Lin S, Zou L, Huang T, Du Z, Hou X, Deng J. Analysis on internal mechanism of zedoary turmeric in treatment of liver cancer based on pharmacodynamic substances and pharmacodynamic groups. Chin Herb Med. 2022;14(4):479\u201393.","journal-title":"Chin Herb Med"},{"issue":"4","key":"265_CR20","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1016\/j.immuni.2007.09.006","volume":"27","author":"EJ Wherry","year":"2007","unstructured":"Wherry EJ, Ha SJ, Kaech SM, Haining WN, Sarkar S, Kalia V, Subramaniam S, Blattman JN, Barber DL, Ahmed R. Molecular signature of CD8\u2009+\u2009T cell exhaustion during chronic viral infection. Immunity. 2007;27(4):670\u201384.","journal-title":"Immunity"},{"issue":"10","key":"265_CR21","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1038\/ni.2703","volume":"14","author":"TF Gajewski","year":"2013","unstructured":"Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol. 2013;14(10):1014\u201322.","journal-title":"Nat Immunol"},{"issue":"6","key":"265_CR22","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1038\/s41590-022-01224-z","volume":"23","author":"JA Belk","year":"2022","unstructured":"Belk JA, Daniel B, Satpathy AT. Epigenetic regulation of T cell exhaustion. Nat Immunol. 2022;23(6):848\u201360.","journal-title":"Nat Immunol"},{"key":"265_CR23","doi-asserted-by":"crossref","unstructured":"Rao RJ, Yang J, Jiang S, El-Khoury W, Hafeez N, Okawa S, Tai YY, Tang Y, Al Aaraj Y, Sembrat J et al. Post-transcriptional regulation of IFI16 promotes inflammatory endothelial pathophenotypes observed in pulmonary arterial hypertension. bioRxiv: the preprint server for biology. 2024.","DOI":"10.1101\/2024.09.19.613988"},{"issue":"6","key":"265_CR24","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1007\/s00262-020-02507-w","volume":"69","author":"M Zhang","year":"2020","unstructured":"Zhang M, Shi Y, Zhang Y, Wang Y, Alotaibi F, Qiu L, Wang H, Peng S, Liu Y, Li Q, et al. miRNA-5119 regulates immune checkpoints in dendritic cells to enhance breast cancer immunotherapy. Cancer Immunol Immunotherapy: CII. 2020;69(6):951\u201367.","journal-title":"Cancer Immunol Immunotherapy: CII"},{"issue":"12","key":"265_CR25","doi-asserted-by":"publisher","first-page":"2043","DOI":"10.1002\/eji.201747041","volume":"47","author":"M van Ham","year":"2017","unstructured":"van Ham M, Teich R, Philipsen L, Niemz J, Amsberg N, Wissing J, Nimtz M, Gr\u00f6be L, Kliche S, Thiel N, et al. TCR signalling network organization at the immunological synapses of murine regulatory T cells. Eur J Immunol. 2017;47(12):2043\u201358.","journal-title":"Eur J Immunol"},{"issue":"1","key":"265_CR26","doi-asserted-by":"publisher","first-page":"4520","DOI":"10.1038\/s41467-020-18298-8","volume":"11","author":"DH Peng","year":"2020","unstructured":"Peng DH, Rodriguez BL, Diao L, Chen L, Wang J, Byers LA, Wei Y, Chapman HA, Yamauchi M, Behrens C, et al. Collagen promotes anti-PD-1\/PD-L1 resistance in cancer through LAIR1-dependent CD8(+) T cell exhaustion. Nat Commun. 2020;11(1):4520.","journal-title":"Nat Commun"},{"issue":"12","key":"265_CR27","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1038\/s43018-020-00133-0","volume":"1","author":"I Solomon","year":"2020","unstructured":"Solomon I, Amann M, Goubier A, Arce Vargas F, Zervas D, Qing C, Henry JY, Ghorani E, Akarca AU, Marafioti T, et al. CD25-T(reg)-depleting antibodies preserving IL-2 signaling on effector T cells enhance effector activation and antitumor immunity. Nat cancer. 2020;1(12):1153\u201366.","journal-title":"Nat cancer"},{"issue":"20","key":"265_CR28","doi-asserted-by":"publisher","first-page":"2696","DOI":"10.1002\/1873-3468.14501","volume":"596","author":"G Liang","year":"2022","unstructured":"Liang G, Feng G, Chen H, Li L, Hu J, Zhou C, Li J, Shen H, Wu F, Tao C, et al. Changes in the TCR repertoire of T-cell subsets during culture of cytokine-induced killer cells. FEBS Lett. 2022;596(20):2696\u2013705.","journal-title":"FEBS Lett"},{"key":"265_CR29","doi-asserted-by":"crossref","unstructured":"Zhang X, Lao M, Xu J, Duan Y, Yang H, Li M, Ying H, He L, Sun K, Guo C et al. Combination cancer immunotherapy targeting TNFR2 and PD-1\/PD-L1 signaling reduces immunosuppressive effects in the microenvironment of pancreatic tumors. J Immunother Cancer. 2022;10(3).","DOI":"10.1136\/jitc-2021-003982"},{"key":"265_CR30","doi-asserted-by":"crossref","unstructured":"Choi H, Cho SY, Schwartz RH, Choi K. Dual effects of Sprouty1 on TCR signaling depending on the differentiation state of the T-cell. Journal of Immunology (Baltimore, Md: 1950). 2006;176(10):6034\u20136045.","DOI":"10.4049\/jimmunol.176.10.6034"},{"key":"265_CR31","doi-asserted-by":"crossref","unstructured":"Ai L, Xu A, Xu J. Roles of PD-1\/PD-L1 pathway: signaling, Cancer, and Beyond. Advances in experimental medicine and biology. 2020;1248:33\u201359.","DOI":"10.1007\/978-981-15-3266-5_3"},{"issue":"12","key":"265_CR32","doi-asserted-by":"publisher","first-page":"110986","DOI":"10.1016\/j.celrep.2022.110986","volume":"39","author":"J Gu","year":"2022","unstructured":"Gu J, Zhou J, Chen Q, Xu X, Gao J, Li X, Shao Q, Zhou B, Zhou H, Wei S, et al. Tumor metabolite lactate promotes tumorigenesis by modulating MOESIN lactylation and enhancing TGF-\u03b2 signaling in regulatory T cells. Cell Rep. 2022;39(12):110986.","journal-title":"Cell Rep"},{"issue":"1","key":"265_CR33","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1165\/rcmb.2016-0037OC","volume":"56","author":"LJ Celada","year":"2017","unstructured":"Celada LJ, Rotsinger JE, Young A, Shaginurova G, Shelton D, Hawkins C, Drake WP. Programmed Death-1 inhibition of phosphatidylinositol 3-Kinase\/AKT\/Mechanistic target of Rapamycin Signaling impairs sarcoidosis CD4(+) T cell proliferation. Am J Respir Cell Mol Biol. 2017;56(1):74\u201382.","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"33","key":"265_CR34","doi-asserted-by":"publisher","first-page":"20159","DOI":"10.1073\/pnas.1918986117","volume":"117","author":"N Li","year":"2020","unstructured":"Li N, Kang Y, Wang L, Huff S, Tang R, Hui H, Agrawal K, Gonzalez GM, Wang Y, Patel SP, et al. ALKBH5 regulates anti-PD-1 therapy response by modulating lactate and suppressive immune cell accumulation in tumor microenvironment. Proc Natl Acad Sci USA. 2020;117(33):20159\u201370.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"1","key":"265_CR35","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1186\/s12943-023-01898-5","volume":"22","author":"M Yue","year":"2023","unstructured":"Yue M, Hu S, Sun H, Tuo B, Jia B, Chen C, Wang W, Liu J, Liu Y, Sun Z, et al. Extracellular vesicles remodel tumor environment for cancer immunotherapy. Mol Cancer. 2023;22(1):203.","journal-title":"Mol Cancer"},{"issue":"2","key":"265_CR36","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.immuni.2016.07.009","volume":"45","author":"NE Scharping","year":"2016","unstructured":"Scharping NE, Menk AV, Moreci RS, Whetstone RD, Dadey RE, Watkins SC, Ferris RL, Delgoffe GM. The Tumor Microenvironment represses T cell mitochondrial Biogenesis to Drive Intratumoral T Cell metabolic insufficiency and dysfunction. Immunity. 2016;45(2):374\u201388.","journal-title":"Immunity"},{"issue":"1","key":"265_CR37","first-page":"79","volume":"14","author":"J Zhai","year":"2021","unstructured":"Zhai J, Song Z, Chang H, Wang Y, Han N, Liu Z, Yin J. He-Wei Granule enhances anti-tumor activity of cyclophosphamide by changing tumor microenvironment. Chin Herb Med. 2021;14(1):79\u201389.","journal-title":"Chin Herb Med"},{"key":"265_CR38","doi-asserted-by":"publisher","first-page":"491","DOI":"10.3389\/fimmu.2019.00491","volume":"10","author":"K Guram","year":"2019","unstructured":"Guram K, Kim SS, Wu V, Sanders PD, Patel S, Schoenberger SP, Cohen EEW, Chen SY, Sharabi AB. A threshold model for T-Cell activation in the era of checkpoint blockade immunotherapy. Front Immunol. 2019;10:491.","journal-title":"Front Immunol"},{"issue":"8","key":"265_CR39","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1038\/nri3862","volume":"15","author":"EJ Wherry","year":"2015","unstructured":"Wherry EJ, Kurachi M. Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol. 2015;15(8):486\u201399.","journal-title":"Nat Rev Immunol"},{"issue":"1","key":"265_CR40","doi-asserted-by":"publisher","first-page":"1956143","DOI":"10.1080\/2162402X.2021.1956143","volume":"10","author":"A Sosnowska","year":"2021","unstructured":"Sosnowska A, Chlebowska-Tuz J, Matryba P, Pilch Z, Greig A, Wolny A, Grzywa TM, Rydzynska Z, Sokolowska O, Rygiel TP, et al. Inhibition of arginase modulates T-cell response in the tumor microenvironment of lung carcinoma. Oncoimmunology. 2021;10(1):1956143.","journal-title":"Oncoimmunology"},{"issue":"6","key":"265_CR41","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1016\/j.cmet.2023.04.017","volume":"35","author":"J Cheng","year":"2023","unstructured":"Cheng J, Yan J, Liu Y, Shi J, Wang H, Zhou H, Zhou Y, Zhang T, Zhao L, Meng X, et al. Cancer-cell-derived fumarate suppresses the anti-tumor capacity of CD8(+) T cells in the tumor microenvironment. Cell Metabol. 2023;35(6):961\u2013e978910.","journal-title":"Cell Metabol"},{"issue":"2","key":"265_CR42","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1158\/0008-5472.CAN-14-1491","volume":"75","author":"M Fletcher","year":"2015","unstructured":"Fletcher M, Ramirez ME, Sierra RA, Raber P, Thevenot P, Al-Khami AA, Sanchez-Pino D, Hernandez C, Wyczechowska DD, Ochoa AC, et al. l-Arginine depletion blunts antitumor T-cell responses by inducing myeloid-derived suppressor cells. Cancer Res. 2015;75(2):275\u201383.","journal-title":"Cancer Res"},{"issue":"4","key":"265_CR43","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.7150\/thno.48101","volume":"11","author":"Y Wen","year":"2021","unstructured":"Wen Y, Hou Y, Yi X, Sun S, Guo J, He X, Li T, Cai J, Wang Z. EZH2 activates CHK1 signaling to promote ovarian cancer chemoresistance by maintaining the properties of cancer stem cells. Theranostics. 2021;11(4):1795\u2013813.","journal-title":"Theranostics"},{"issue":"1","key":"265_CR44","first-page":"445","volume":"21","author":"M Liu","year":"2020","unstructured":"Liu M, Li Z, Yao W, Zeng X, Wang L, Cheng J, Ma B, Zhang R, Min W, Wang H. IDO inhibitor synergized with radiotherapy to delay tumor growth by reversing T cell exhaustion. Mol Med Rep. 2020;21(1):445\u201353.","journal-title":"Mol Med Rep"},{"issue":"1","key":"265_CR45","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1186\/s12967-022-03480-x","volume":"20","author":"L Liu","year":"2022","unstructured":"Liu L, Wang A, Liu X, Han S, Sun Y, Zhang J, Guo L, Zhang Y. Blocking TIGIT\/CD155 signalling reverses CD8(+) T cell exhaustion and enhances the antitumor activity in cervical cancer. J Translational Med. 2022;20(1):280.","journal-title":"J Translational Med"},{"issue":"1","key":"265_CR46","doi-asserted-by":"publisher","first-page":"e12803","DOI":"10.1111\/jpi.12803","volume":"73","author":"L He","year":"2022","unstructured":"He L, Fan Y, Zhang Y, Tu T, Zhang Q, Yuan F, Cheng C. Single-cell transcriptomic analysis reveals circadian rhythm disruption associated with poor prognosis and drug-resistance in lung adenocarcinoma. J Pineal Res. 2022;73(1):e12803.","journal-title":"J Pineal Res"},{"issue":"7710","key":"265_CR47","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1038\/s41586-018-0206-z","volume":"558","author":"N Chihara","year":"2018","unstructured":"Chihara N, Madi A, Kondo T, Zhang H, Acharya N, Singer M, Nyman J, Marjanovic ND, Kowalczyk MS, Wang C, et al. Induction and transcriptional regulation of the co-inhibitory gene module in T cells. Nature. 2018;558(7710):454\u20139.","journal-title":"Nature"},{"issue":"7","key":"265_CR48","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1016\/j.cell.2017.05.035","volume":"169","author":"C Zheng","year":"2017","unstructured":"Zheng C, Zheng L, Yoo JK, Guo H, Zhang Y, Guo X, Kang B, Hu R, Huang JY, Zhang Q, et al. Landscape of infiltrating T cells in Liver Cancer revealed by single-cell sequencing. Cell. 2017;169(7):1342\u2013e13561316.","journal-title":"Cell"},{"issue":"25","key":"265_CR49","doi-asserted-by":"publisher","first-page":"12410","DOI":"10.1073\/pnas.1905675116","volume":"116","author":"H Seo","year":"2019","unstructured":"Seo H, Chen J, Gonz\u00e1lez-Avalos E, Samaniego-Castruita D, Das A, Wang YH, L\u00f3pez-Moyado IF, Georges RO, Zhang W, Onodera A, et al. TOX and TOX2 transcription factors cooperate with NR4A transcription factors to impose CD8(+) T cell exhaustion. Proc Natl Acad Sci USA. 2019;116(25):12410\u20135.","journal-title":"Proc Natl Acad Sci USA"},{"issue":"7749","key":"265_CR50","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1038\/s41586-019-0985-x","volume":"567","author":"J Chen","year":"2019","unstructured":"Chen J, L\u00f3pez-Moyado IF, Seo H, Lio CJ, Hempleman LJ, Sekiya T, Yoshimura A, Scott-Browne JP, Rao A. NR4A transcription factors limit CAR T cell function in solid tumours. Nature. 2019;567(7749):530\u20134.","journal-title":"Nature"},{"issue":"7","key":"265_CR51","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1016\/j.ccell.2022.06.001","volume":"40","author":"JA Belk","year":"2022","unstructured":"Belk JA, Yao W, Ly N, Freitas KA, Chen YT, Shi Q, Valencia AM, Shifrut E, Kale N, Yost KE, et al. Genome-wide CRISPR screens of T cell exhaustion identify chromatin remodeling factors that limit T cell persistence. Cancer Cell. 2022;40(7):768\u2013e786767.","journal-title":"Cancer Cell"},{"issue":"2","key":"265_CR52","doi-asserted-by":"publisher","first-page":"e1082707","DOI":"10.1080\/2162402X.2015.1082707","volume":"5","author":"G Verdeil","year":"2016","unstructured":"Verdeil G. MAF drives CD8(+) T-cell exhaustion. Oncoimmunology. 2016;5(2):e1082707.","journal-title":"Oncoimmunology"},{"issue":"7764","key":"265_CR53","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/s41586-019-1325-x","volume":"571","author":"O Khan","year":"2019","unstructured":"Khan O, Giles JR, McDonald S, Manne S, Ngiow SF, Patel KP, Werner MT, Huang AC, Alexander KA, Wu JE, et al. TOX transcriptionally and epigenetically programs CD8(+) T cell exhaustion. Nature. 2019;571(7764):211\u20138.","journal-title":"Nature"},{"issue":"1","key":"265_CR54","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.cell.2016.09.006","volume":"167","author":"A Amabile","year":"2016","unstructured":"Amabile A, Migliara A, Capasso P, Biffi M, Cittaro D, Naldini L, Lombardo A. Inheritable silencing of endogenous genes by hit-and-run targeted epigenetic editing. Cell. 2016;167(1):219\u2013e232214.","journal-title":"Cell"},{"issue":"4","key":"265_CR55","first-page":"576","volume":"14","author":"M Lei","year":"2022","unstructured":"Lei M, Chen N, Xu Y, Gong Q, Gao J. Lithocarpus Polystachyus (Sweet Tea) water extract promotes human hepatocytes HL7702 proliferation through activation of HGF\/AKT\/ERK signaling pathway. Chin Herb Med. 2022;14(4):576\u201382.","journal-title":"Chin Herb Med"},{"key":"265_CR56","doi-asserted-by":"crossref","unstructured":"Jones DM, Read KA, Oestreich KJ. Dynamic roles for IL-2-STAT5 signaling in effector and regulatory CD4(+) T cell Populations. Journal of immunology (Baltimore, Md: 1950). 2020;205(7):1721\u20131730.","DOI":"10.4049\/jimmunol.2000612"},{"issue":"4","key":"265_CR57","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/j.immuni.2015.04.005","volume":"42","author":"EC Rosser","year":"2015","unstructured":"Rosser EC, Mauri C. Regulatory B cells: origin, phenotype, and function. Immunity. 2015;42(4):607\u201312.","journal-title":"Immunity"},{"issue":"2","key":"265_CR58","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1053\/j.gastro.2021.04.041","volume":"161","author":"Y Lu","year":"2021","unstructured":"Lu Y, Li Y, Liu Q, Tian N, Du P, Zhu F, Han Y, Liu X, Liu X, Peng X, et al. MondoA-Thioredoxin-interacting protein Axis maintains Regulatory T-Cell identity and function in Colorectal Cancer Microenvironment. Gastroenterology. 2021;161(2):575\u2013e591516.","journal-title":"Gastroenterology"},{"key":"265_CR59","doi-asserted-by":"crossref","unstructured":"Fitzgerald AA, Wang S, Agarwal V, Marcisak EF, Zuo A, Jablonski SA, Loth M, Fertig EJ, MacDougall J, Zhukovsky E et al. DPP inhibition alters the CXCR3 axis and enhances NK and CD8\u2009+\u2009T cell infiltration to improve anti-PD1 efficacy in murine models of pancreatic ductal adenocarcinoma. J Immunother Cancer. 2021;9(11).","DOI":"10.1136\/jitc-2021-002837"},{"issue":"7728","key":"265_CR60","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1038\/s41586-018-0615-z","volume":"562","author":"M Deng","year":"2018","unstructured":"Deng M, Gui X, Kim J, Xie L, Chen W, Li Z, He L, Chen Y, Chen H, Luo W, et al. LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration. Nature. 2018;562(7728):605\u20139.","journal-title":"Nature"},{"key":"265_CR61","doi-asserted-by":"crossref","unstructured":"Saka D, G\u00f6kalp M, Piyade B, Cevik NC, Arik Sever E, Unutmaz D, Ceyhan GO, Demir IE, Asimgil H. Mechanisms of T-Cell exhaustion in pancreatic Cancer. Cancers. 2020;12(8).","DOI":"10.3390\/cancers12082274"},{"issue":"1","key":"265_CR62","doi-asserted-by":"publisher","first-page":"2033528","DOI":"10.1080\/2162402X.2022.2033528","volume":"11","author":"TLA Wachsmann","year":"2022","unstructured":"Wachsmann TLA, Wouters AK, Remst DFG, Hagedoorn RS, Meeuwsen MH, van Diest E, Leusen J, Kuball J, Falkenburg JHF, Heemskerk MHM. Comparing CAR and TCR engineered T cell performance as a function of tumor cell exposure. Oncoimmunology. 2022;11(1):2033528.","journal-title":"Oncoimmunology"},{"key":"265_CR63","doi-asserted-by":"publisher","first-page":"430861","DOI":"10.1155\/2013\/430861","volume":"2013","author":"MF Zhao","year":"2013","unstructured":"Zhao MF, Qu XJ, Qu JL, Jiang YH, Zhang Y, Hou KZ, Deng H, Liu YP. The role of E3 ubiquitin ligase cbl proteins in interleukin-2-induced Jurkat T-cell activation. Biomed Res Int. 2013;2013:430861.","journal-title":"Biomed Res Int"},{"issue":"4","key":"265_CR64","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1159\/000067596","volume":"129","author":"MK Levings","year":"2002","unstructured":"Levings MK, Bacchetta R, Schulz U, Roncarolo MG. The role of IL-10 and TGF-beta in the differentiation and effector function of T regulatory cells. Int Arch Allergy Immunol. 2002;129(4):263\u201376.","journal-title":"Int Arch Allergy Immunol"},{"issue":"3","key":"265_CR65","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1038\/s41423-019-0321-2","volume":"17","author":"Z Li","year":"2020","unstructured":"Li Z, Deng M, Huang F, Jin C, Sun S, Chen H, Liu X, He L, Sadek AH, Zhang CC. LILRB4 ITIMs mediate the T cell suppression and infiltration of acute myeloid leukemia cells. Cell Mol Immunol. 2020;17(3):272\u201382.","journal-title":"Cell Mol Immunol"},{"issue":"11","key":"265_CR66","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1038\/s41419-023-06245-6","volume":"14","author":"Y Liu","year":"2023","unstructured":"Liu Y, Wang X, Liu Y, Yang J, Mao W, Feng C, Wu X, Chen X, Chen L, Dong P. N4-acetylcytidine-dependent GLMP mRNA stabilization by NAT10 promotes head and neck squamous cell carcinoma metastasis and remodels tumor microenvironment through MAPK\/ERK signaling pathway. Cell Death Dis. 2023;14(11):712.","journal-title":"Cell Death Dis"},{"issue":"10","key":"265_CR67","doi-asserted-by":"publisher","first-page":"2764","DOI":"10.1158\/1078-0432.CCR-20-3863","volume":"27","author":"Y Hu","year":"2021","unstructured":"Hu Y, Zhou Y, Zhang M, Ge W, Li Y, Yang L, Wei G, Han L, Wang H, Yu S, et al. CRISPR\/Cas9-Engineered Universal CD19\/CD22 Dual-targeted CAR-T cell therapy for Relapsed\/Refractory B-cell Acute Lymphoblastic Leukemia. Clin cancer Research: Official J Am Association Cancer Res. 2021;27(10):2764\u201372.","journal-title":"Clin cancer Research: Official J Am Association Cancer Res"},{"issue":"1","key":"265_CR68","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1182\/blood.2021013648","volume":"140","author":"PM Maciocia","year":"2022","unstructured":"Maciocia PM, Wawrzyniecka PA, Maciocia NC, Burley A, Karpanasamy T, Devereaux S, Hoekx M, O\u2019Connor D, Leon T, Rapoz-D\u2019Silva T, et al. Anti-CCR9 chimeric antigen receptor T cells for T-cell acute lymphoblastic leukemia. Blood. 2022;140(1):25\u201337.","journal-title":"Blood"},{"issue":"5","key":"265_CR69","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1016\/j.ymthe.2017.03.010","volume":"25","author":"C Zhang","year":"2017","unstructured":"Zhang C, Wang Z, Yang Z, Wang M, Li S, Li Y, Zhang R, Xiong Z, Wei Z, Shen J, et al. Phase I escalating-dose trial of CAR-T therapy targeting CEA(+) metastatic colorectal cancers. Mol Therapy: J Am Soc Gene Therapy. 2017;25(5):1248\u201358.","journal-title":"Mol Therapy: J Am Soc Gene Therapy"},{"issue":"12","key":"265_CR70","doi-asserted-by":"publisher","first-page":"4910","DOI":"10.1007\/s12325-020-01509-5","volume":"37","author":"RR McKay","year":"2020","unstructured":"McKay RR, Hafron JM, Ferro C, Wilfehrt HM, Fitch K, Flanders SC, Fabrizio MD, Schweizer MT. A Retrospective Observational Analysis of Overall Survival with Sipuleucel-T in Medicare Beneficiaries Treated for advanced prostate Cancer. Adv Therapy. 2020;37(12):4910\u201329.","journal-title":"Adv Therapy"},{"key":"265_CR71","doi-asserted-by":"publisher","first-page":"5699","DOI":"10.2147\/CMAR.S286917","volume":"13","author":"J Kleemann","year":"2021","unstructured":"Kleemann J, J\u00e4ger M, Valesky E, Kippenberger S, Kaufmann R, Meissner M. Real-world experience of Talimogene Laherparepvec (T-VEC) in Old and Oldest-Old patients with Melanoma: a retrospective single Center Study. Cancer Manage Res. 2021;13:5699\u2013709.","journal-title":"Cancer Manage Res"},{"issue":"4","key":"265_CR72","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1038\/s41391-019-0144-3","volume":"22","author":"EK Holl","year":"2019","unstructured":"Holl EK, McNamara MA, Healy P, Anand M, Concepcion RS, Breland CD, Dumbudze I, Tutrone R, Shore N, Armstrong AJ, et al. Prolonged PSA stabilization and overall survival following sipuleucel-T monotherapy in metastatic castration-resistant prostate cancer patients. Prostate Cancer Prostatic Dis. 2019;22(4):588\u201392.","journal-title":"Prostate Cancer Prostatic Dis"},{"issue":"12","key":"265_CR73","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.1080\/14712598.2022.1998450","volume":"21","author":"M Fazel","year":"2021","unstructured":"Fazel M, AlRawashdh N, Alamer A, Curiel-Lewandrowski C, Abraham I. Is there still a role for talimogene laherparepvec (T-VEC) in advanced melanoma? An indirect efficacy comparison of T-VEC plus ipilimumab combination therapy versus T-VEC alone as salvage therapy in unresectable metastatic melanoma. Expert Opin Biol Ther. 2021;21(12):1647\u201353.","journal-title":"Expert Opin Biol Ther"},{"issue":"10","key":"265_CR74","doi-asserted-by":"publisher","first-page":"e521","DOI":"10.1016\/S2352-3026(19)30115-2","volume":"6","author":"Z Yan","year":"2019","unstructured":"Yan Z, Cao J, Cheng H, Qiao J, Zhang H, Wang Y, Shi M, Lan J, Fei X, Jin L, et al. A combination of humanised anti-CD19 and anti-BCMA CAR T cells in patients with relapsed or refractory multiple myeloma: a single-arm, phase 2 trial. Lancet Haematol. 2019;6(10):e521\u20139.","journal-title":"Lancet Haematol"},{"issue":"7","key":"265_CR75","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1158\/2159-8290.CD-16-1184","volume":"7","author":"D Ajona","year":"2017","unstructured":"Ajona D, Ortiz-Espinosa S, Moreno H, Lozano T, Pajares MJ, Agorreta J, B\u00e9rtolo C, Lasarte JJ, Vicent S, Hoehlig K, et al. A combined PD-1\/C5a blockade synergistically protects against Lung Cancer Growth and Metastasis. Cancer Discov. 2017;7(7):694\u2013703.","journal-title":"Cancer Discov"}],"container-title":["Biological Procedures Online"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12575-025-00265-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12575-025-00265-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12575-025-00265-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T10:38:35Z","timestamp":1738665515000},"score":1,"resource":{"primary":{"URL":"https:\/\/biologicalproceduresonline.biomedcentral.com\/articles\/10.1186\/s12575-025-00265-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,4]]},"references-count":75,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["265"],"URL":"https:\/\/doi.org\/10.1186\/s12575-025-00265-6","relation":{},"ISSN":["1480-9222"],"issn-type":[{"value":"1480-9222","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,4]]},"assertion":[{"value":"10 November 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 January 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 February 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval"}},{"value":"The manuscript has been approved for publication by all authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for Publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"5"}}