T Cell Dysfunction and Exhaustion in Cancer
Open accessAbstract
Tumor immunotherapy is a promising therapeutic strategy for patients with advanced cancers. T cells are key mediators of antitumor function that specifically recognize and react to tumor-expressing antigens and have proven critical for cancer immunotherapy. However, T cells are not as effective against cancer as expected. This is partly because T cells enter a dysfunctional or exhausted state, which is characterized by sustained expression of inhibitory receptors and a transcriptional state distinct from that of functional effector or memory T cells. T cell dysfunction induces the out of control of tumors. Recently, T cell dysfunction has been investigated in many experimental and clinical settings. The molecular definition of T cell dysfunction and the underlying causes of the T cell dysfunction has been advanced regardless of the fact that the pathways involved are not well elucidated, which proposing promising therapeutic opportunities in clinic. In this review, we will discuss the recent advances in the molecular mechanisms that affect TME and induce T cell dysfunction, and the development of promising immunotherapies to counteract the mechanisms of tumor-induced T cell dysfunction. Better understanding these underlying mechanisms may lead to new strategies to improve the clinical outcome of patients with cancer.
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T cell senescence is irreversible, whereas anergy and exhaustion are considered reversible.
“T cell senescence is irreversible, as opposed to their anergy and exhaustion, both of which are considered reversible [31, 38–40].”
From Immunosenescence: a key player in cancer development (2020) · cites this paper as [40]
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“, AMPK, Myc, HIF-1α and mTOR) that control T cell differentiation have been highlighted as a novel therapeutic targets for immune modulation (Chang and Pearce, 2016).”
BackgroundVerma, V., Shrimali, R. K., Ahmad, S., Dai, W., Wang, H., Lu, S., Nandre, R., Gaur, P., Lopez, J., Sade-Feldman, M., et al. (2019) · Nature Immunology · doi:10.1038/s41590-019-0441-y · Cited by 333 · cited 1× · see citing works
“Some studies suggest that the efficacy of immunotherapy is limited by the generation of dysfunctional T cells in the tumor microenvironment (TME) (Thommen and Schumacher, 2018; Vodnala et al., 2019).”
BackgroundReactive Oxygen Species Regulate T Cell Immune Response in the Tumor Microenvironment
Chen, X., Song, M., Zhang, B., & Zhang, Y. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/1580967 · Cited by 326 · cited 1× · see citing works
“ROS produced by MDSCs and other cells may interact with T cells and cause oxidative stress which may induce CD8 T cell hypo-responsiveness in cancer (Chen et al., 2016).”
BackgroundSelf-citationChimeric antigen receptor T cells: a novel therapy for solid tumors
Yu, S., Li, A., Liu, Q., Li, T., Yuan, X., Han, X., & Wu, K. (2017) · Journal of Hematology & Oncology · doi:10.1186/s13045-017-0444-9 · Cited by 306 · cited 1× · see citing works
“However, despite extensive research, the efficacy of CAR-T cell therapy on controlling solid tumors is limited effects due to the influence of TME (Yu et al., 2017; Li et al., 2018d; Yan et al., 2019).”
BackgroundLi, J., Wang, L., Chen, X., Li, L., Li, Y., Ping, Y., Huang, L., Yue, D., Zhang, Z., Wang, F., et al. (2017) · OncoImmunology · doi:10.1080/2162402x.2017.1320011 · Cited by 299 · cited 1× · see citing works
“Moreover, TGF-β stimulates CD39 and CD73 expression, thereby inhibiting autologous CD8+ T cell proliferation and function (Li et al., 2017).”
BackgroundSelf-citationStone, M. L., Chiappinelli, K. B., Li, H., Murphy, L. M., Travers, M. E., Topper, M. J., Mathios, D., Lim, M. K., Shih, I., Wang, T., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1712514114 · Cited by 290 · see citing works
Wang, X., He, Q., Shen, H., Xia, A., Tian, W., Yu, W., & Sun, B. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2019.05.015 · Cited by 287 · see citing works
Reprogramming the tumor microenvironment: tumor-induced immunosuppressive factors paralyze T cells
Wu, A. A., Drake, V. E., Huang, H.-S., Chiu, S., & Zheng, L. (2015) · OncoImmunology · doi:10.1080/2162402x.2015.1016700 · Cited by 274 · cited 1× · see citing works
“In addition, NO alone can suppress CD8 T cells by inhibiting the phosphorylation and activation of JAK3 and STAT5 transcription factors, as well as inducing T-cell apoptosis (Wu et al., 2015).”
BackgroundNagarsheth, N., Peng, D., Kryczek, I., Wu, K., Li, W., Zhao, E., Zhao, L., Wei, S., Frankel, T. L., Vatan, L., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-15-1938 · Cited by 270 · cited 16× · see citing works
“The ARG1, iNOS, TGF-β and ROS are secreted by MDSCs or TAMs and induce CD8+ T cell dysfunction.”
InfluentialLi, L., Wang, L., Li, J., Fan, Z., Li, Y., Zhang, Z., Zhang, C., Yue, D., Qin, G., Zhang, T., et al. (2018) · Cancer Research · doi:10.1158/0008-5472.can-17-2460 · Cited by 266 · see citing works
Self-citationBoyiadzis, M. M., Dhodapkar, M. V., Brentjens, R. J., Kochenderfer, J. N., Neelapu, S. S., Maus, M. V., Porter, D. L., Maloney, D. G., Grupp, S. A., Mackall, C. L., et al. (2018) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-018-0460-5 · Cited by 249 · cited 2× · see citing works
“…neoantigen vaccines and checkpoint blockade therapies using anti-programed cell death 1 (PD-1) and anti-PD-ligand 1 (PD-L1) have shown potent therapeutic effects in patients with advanced cancer (Chapuis et al., 2016b; Yee and Lizee, 2017; Boyiadzis et al., 2018; Yee, 2018; Riley et al., 2019).”
BackgroundGenetic and Epigenetic Regulation of PD-1 Expression
Bally, A. P. R., Austin, J. W., & Boss, J. M. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1502643 · Cited by 245 · cited 1× · see citing works
“When TCR stimulation and IL-6 or IL-12 treatment were combined, both H3K4me1 and H3K27 acetylation were contributed to increased PD-1 expression (Bally et al., 2016).”
BackgroundLi, J., Li, W., Huang, K., Zhang, Y., Kupfer, G. M., & Zhao, Q. (2018) · Journal of Hematology & Oncology · doi:10.1186/s13045-018-0568-6 · Cited by 245 · see citing works
Self-citationHigh Levels of Eomes Promote Exhaustion of Anti-tumor CD8+ T Cells
Li, J., He, Y., Hao, J., Ni, L., & Dong, C. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02981 · Cited by 223 · see citing works
Brooks, D. G., Ha, S., Elsaesser, H. J., Sharpe, A. H., Freeman, G. J., & Oldstone, M. B. A. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811139106 · Cited by 220 · cited 1× · see citing works
“Thus, IL-10 and PD-1 pathways act synergistically through distinct pathways to suppress T cell survival and function (Brooks et al., 2008).”
BackgroundZhen, Z., Tang, W., Wang, M., Zhou, S., Wang, H., Wu, Z., Hao, Z., Li, Z., Liu, L., & Xie, J. (2016) · Nano Letters · doi:10.1021/acs.nanolett.6b04150 · Cited by 218 · cited 1× · see citing works
“They can also polarize these recruited myeloid cells toward the M2 phenotype (Zhen et al., 2017).”
BackgroundChimeric antigen receptor T-cell therapies for multiple myeloma
Mikkilineni, L., & Kochenderfer, J. N. (2017) · Blood · doi:10.1182/blood-2017-06-793869 · Cited by 213 · cited 1× · see citing works
“For example, treatment with anti-PD-1/PD-L1 and anti-CTLA4 immune checkpoint inhibitors reinvigorate dysfunctional TILs and augment their anti-tumor effects (Wherry and Kurachi, 2015; Zarour, 2016; Miller et al., 2019; Wang et al., 2019a).”
MethodmTOR Regulation of Glycolytic Metabolism in T Cells
Salmond, R. J. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00122 · Cited by 211 · cited 1× · see citing works
“However, when antigen-experienced T cells are chronically exposed to the same antigen, substantial alterations in T cell activation and differentiation may occur, leading to T cell “dysfunction” or “exhaustion” (Wherry, 2011; Schietinger and Greenberg, 2014).”
BackgroundLi, J., Lee, Y., Li, Y., Jiang, Y. Y., Lu, H., Zang, W., Zhao, X., Liu, L., Chen, Y., Tan, H., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.03.018 · Cited by 210 · see citing works
Emerging strategies for combination checkpoint modulators in cancer immunotherapy
Popović, A., Jaffee, E. M., & Zaidi, N. (2018) · Journal of Clinical Investigation · doi:10.1172/jci120775 · Cited by 209 · cited 1× · see citing works
“Intriguingly, BATF, a transcription factor of the AP-1 family, was found to impair T cell proliferation and cytokine secretion during HIV infection in a pathway downstream of PD-1 (Quigley et al., 2010).”
BackgroundMetabolic Barriers to T Cell Function in Tumors
Sugiura, A., & Rathmell, J. C. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1701041 · Cited by 208 · cited 2× · see citing works
“However, activated and functional CD8+ T cells can also overexpress PD-1 in cancer patients (Fourcade et al., 2010), and not all PD-1+ cells might respond equally to anti-PD-1 therapy (Thommen et al., 2018).”
BackgroundMa, R., Ji, T., Zhang, Y., Dong, W., Chen, X., Xu, P., Chen, D., Liang, X., Yin, X., Liu, Y., et al. (2017) · Nature Cell Biology · doi:10.1038/s41556-017-0002-2 · Cited by 207 · cited 1× · see citing works
“A previous study demonstrated that the abrogation of phosphoenolpyruvate carboxykinase (Pck1)–glycogen–pentose phosphate pathway (PPP) decreases GSH/GSSG ratios and increases levels of ROS levels, leading to impairment of memory CD8+ T cell formation (Ma et al., 2018).”
BackgroundSelf-citationCassetta, L., & Kitamura, T. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00038 · Cited by 200 · cited 1× · see citing works
“An anti-CSF1R antibody was shown to reprogram TAM polarization and improve the responses to ICB therapy in pancreatic cancer (Cassetta and Kitamura, 2018).”
BackgroundBenner, B. N., Scarberry, L., Suarez‐Kelly, L. P., Duggan, M. C., Campbell, A. R., Smith, E., Lapurga, G., Jiang, K., Butchar, J. P., Tridandapani, S., et al. (2019) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-019-0622-0 · Cited by 185 · cited 15× · see citing works
“The ARG1, iNOS, TGF-β and ROS are secreted by MDSCs or TAMs and induce CD8+ T cell dysfunction.”
BackgroundInfluentialWang, D., Yang, L., Yue, D., Cao, L., Li, L., Wang, D., Ping, Y., Shen, Z., Zheng, Y., Wang, L., et al. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.03.040 · Cited by 183 · see citing works
Self-citationWang, B., Zhang, W., Jankovic, V., Golubov, J., Poon, P., Oswald, E. M., Gurer, C., Wei, J., Ramos, I., Wu, Q., et al. (2018) · Science Immunology · doi:10.1126/sciimmunol.aat7061 · Cited by 167 · see citing works
The role of AMPK in T cell metabolism and function
Ma, E. H., Poffenberger, M. C., Wong, A., & Jones, R. G. (2017) · Current Opinion in Immunology · doi:10.1016/j.coi.2017.04.004 · Cited by 154 · see citing works
Targeting T Cell Metabolism for Improvement of Cancer Immunotherapy
Bourgeois, T. L., Strauss, L., Aksoylar, H., Daneshmandi, S., Seth, P., Patsoukis, N., & Boussiotis, V. A. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00237 · Cited by 152 · see citing works
CAR T-Cell Therapies in Glioblastoma: A First Look
Migliorini, D., Dietrich, P.-Y., Stupp, R., Linette, G. P., Posey, A. D., & June, C. H. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-2871 · Cited by 131 · see citing works
He, S., Liu, Y., Meng, L., Sun, H., Wang, Y., Ji, Y., Purushe, J., Chen, P., Li, C., Madžo, J., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-02187-8 · Cited by 129 · see citing works
Self-citationChapuis, A. G., Roberts, I. M., Thompson, J. A., Margolin, K. A., Bhatia, S., Lee, S. M., Sloan, H. L., Lai, I. P., Farrar, E. A., Wagener, F. D., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2015.65.5142 · Cited by 122 · cited 2× · see citing works
“…neoantigen vaccines and checkpoint blockade therapies using anti-programed cell death 1 (PD-1) and anti-PD-ligand 1 (PD-L1) have shown potent therapeutic effects in patients with advanced cancer (Chapuis et al., 2016b; Yee and Lizee, 2017; Boyiadzis et al., 2018; Yee, 2018; Riley et al., 2019).”
BackgroundYan, Z.-X., Li, L., Wang, W., OuYang, B.-S., Cheng, S., Wang, L., Wu, W., Xu, P.-P., Muftuoglu, M., Hao, M., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-0101 · Cited by 115 · cited 1× · see citing works
“However, despite extensive research, the efficacy of CAR-T cell therapy on controlling solid tumors is limited effects due to the influence of TME (Yu et al., 2017; Li et al., 2018d; Yan et al., 2019).”
BackgroundHistone Methyltransferase EZH2: A Therapeutic Target for Ovarian Cancer
Jones, B. A., Varambally, S., & Arend, R. C. (2018) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-17-0437 · Cited by 115 · cited 1× · see citing works
“Interestingly, inhibition of EZH2 in ovarian and colorectal cancer patients resulted in increased of CXCL9 and CXCL10 production and augmented the infiltration of T cells that eliminate tumors (Nagarsheth et al., 2016; Jones et al., 2018).”
BackgroundAmbade, A., Satishchandran, A., Saha, B., Gyöngyösi, B., Lowe, P., Kodys, K., Catalano, D. E., & Szabó, G. (2016) · OncoImmunology · doi:10.1080/2162402x.2016.1221557 · Cited by 96 · cited 1× · see citing works
“They also have strong microbicidal and tumoricidal activity (Sica and Mantovani, 2012; Ambade et al., 2016).”
BackgroundLi, Y., Wang, F., Wang, L., Huang, L. J., Wang, J., Zhang, B., & Zhang, Y. (2015) · Oncotarget · doi:10.18632/oncotarget.3547 · Cited by 93 · cited 2× · see citing works
“This effect primarily relies on activation of toll like receptor 4 (TLR4) (Yang et al., 2015).”
BackgroundSelf-citationBlimp-1–mediated CD4 T cell exhaustion causes CD8 T cell dysfunction during chronic toxoplasmosis
Hwang, S., Cobb, D. A., Bhadra, R., Youngblood, B., & Khan, I. A. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20151995 · Cited by 91 · cited 1× · see citing works
“Similarly, Blimp-1 was found to drive T cells toward a dysfunctional phenotype during chronic LCMV infection (Hwang et al., 2016).”
BackgroundCombination regimens with PD-1/PD-L1 immune checkpoint inhibitors for gastrointestinal malignancies
Wang, D., Lin, J., Yang, X., Long, J., Bai, Y., Yang, X., Mao, Y., Sang, X., Seery, S., & Zhao, H. (2019) · Journal of Hematology & Oncology · doi:10.1186/s13045-019-0730-9 · Cited by 89 · see citing works
Molecular and clinical characterization of CD163 expression via large-scale analysis in glioma
Liu, S., Zhang, C., Maimela, N. R., Li, Y., Zhang, Z., Yü, P., Huang, L. J., & Zhang, Y. (2019) · OncoImmunology · doi:10.1080/2162402x.2019.1601478 · Cited by 88 · see citing works
Self-citationJi, Y., Fioravanti, J., Zhu, W., Wang, H., Wu, T., Hu, J., Lacey, N. E., Gautam, S., Gall, J. B. L., Yang, X., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09882-8 · Cited by 87 · see citing works
Self-citationSuppression of T cells by myeloid-derived suppressor cells in cancer
Chen, J., Ye, Y., Liu, P., Yu, W., Wei, F., Li, H., & Yu, J. (2016) · Human Immunology · doi:10.1016/j.humimm.2016.12.001 · Cited by 87 · see citing works
Chapuis, A. G., Lee, S. M., Thompson, J. A., Roberts, I. M., Margolin, K. A., Bhatia, S., Sloan, H. L., Lai, I. P., Wagener, F. D., Shibuya, K. C., et al. (2016) · The Journal of Experimental Medicine · doi:10.1084/jem.20152021 · Cited by 86 · see citing works
miR-143 Regulates Memory T Cell Differentiation by Reprogramming T Cell Metabolism
Zhang, T., Zhang, Z., Li, F., Ping, Y., Qin, G., Zhang, C., & Zhang, Y. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1800230 · Cited by 82 · cited 1× · see citing works
“Our previous work demonstrated that miR-143 enhances the anti-tumor effects of CD8+ T cells by promoting memory T cell differentiation and metabolism reprograming by inhibiting of glycolysis targeting glucose transporter-1 (Glut-1) (Zhang et al., 2018).”
BackgroundSelf-citationIsolation of Mouse and Human Tumor-Associated Macrophages
Cassetta, L., Noy, R., Swierczak, A., Sugano, G., Smith, H. O., Wiechmann, L., & Pollard, J. W. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-26666-4_12 · Cited by 80 · cited 15× · see citing works
“The ARG1, iNOS, TGF-β and ROS are secreted by MDSCs or TAMs and induce CD8+ T cell dysfunction.”
BackgroundInfluentialBohrer, L. R., Chen, D., Hallstrom, T. C., & Huang, H. (2010) · Endocrinology · doi:10.1210/en.2010-0436 · Cited by 75 · cited 1× · see citing works
“EZH2 represses the expression of tumor suppressor genes in various cancer cells, thereby promoting cell invasion and driving tumor progression (Bohrer et al., 2010; Hayashi et al., 2011).”
BackgroundEngineering Chimeric Antigen Receptor T-Cells for Racing in Solid Tumors: Don’t Forget the Fuel
Irving, M. B., de Silly, R. V., Scholten, K. B. J., Dilek, N., & Coukos, G. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00267 · Cited by 74 · see citing works
Tick-TOX, it’s time for T cell exhaustion
Mann, T. H., & Kaech, S. M. (2019) · Nature Immunology · doi:10.1038/s41590-019-0478-y · Cited by 69 · cited 1× · see citing works
“The Transcription factors such as HIF-1α, NR4A1, TOX, Eomes, T-bet, Blimp-1, NFAT and BATF regulate PD-1 expression and have been implicated in T cell exhaustion and dysfunction. exhaustion) in both CD4+ and CD8+ T cells, if it does not bind AP-1 transcription factors (Martinez et al., 2015).”
BackgroundNFκB–Pim-1–Eomesodermin axis is critical for maintaining CD8 T-cell memory quality
Knudson, K. M., Pritzl, C. J., Saxena, V., Altman, A., Daniëls, M. A., & Teixeiro, E. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1608448114 · Cited by 62 · cited 1× · see citing works
“In contrast, Eomes is highly expressed in memory T cells and is considered important for the maintenance of memory T cells (Knudson et al., 2017).”
BackgroundPersonalized cancer neoantigen vaccines come of age
Chu, Y., Liu, Q., Wei, J., & Liu, B. (2018) · Theranostics · doi:10.7150/thno.24387 · Cited by 62 · see citing works
Molecular dissection of CD8+ T cell dysfunction
Wang, C., Singer, M., & Anderson, A. (2017) · Trends in immunology · doi:10.1016/j.it.2017.05.008 · Cited by 57 · see citing works
Therapeutic Cancer Vaccines—T Cell Responses and Epigenetic Modulation
Kartikasari, A. E. R., Prakash, M. D., Cox, M., Wilson, K., Boer, J. C., Cauchi, J. A., & Plebanski, M. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2018.03109 · Cited by 54 · see citing works
Adoptive T cell therapy: points to consider
Yee, C. (2018) · Current Opinion in Immunology · doi:10.1016/j.coi.2018.04.007 · Cited by 52 · cited 2× · see citing works
“…neoantigen vaccines and checkpoint blockade therapies using anti-programed cell death 1 (PD-1) and anti-PD-ligand 1 (PD-L1) have shown potent therapeutic effects in patients with advanced cancer (Chapuis et al., 2016b; Yee and Lizee, 2017; Boyiadzis et al., 2018; Yee, 2018; Riley et al., 2019).”
BackgroundLi, L., Ma, Y., & Xu, Y. (2019) · International Immunopharmacology · doi:10.1016/j.intimp.2018.12.051 · Cited by 51 · see citing works
Wang, X., Brea, L. T., & Yu, J. (2019) · PubMed Central · Cited by 42 · see citing works
Regulation of T cell differentiation and function by epigenetic modification enzymes
Liu, H., Li, P., Wei, Z., Zhang, C., Xia, M., Du, Q., Chen, Y., Liu, N., Li, H., & Yang, X. (2019) · Seminars in Immunopathology · doi:10.1007/s00281-019-00731-w · Cited by 37 · see citing works
Hayashi, S., Kumai, T., Matsuda, Y., Aoki, N., Sato, K., Kimura, S., Kitada, M., Tateno, M., Celis, E., & Kobayashi, H. (2011) · Journal of Translational Medicine · doi:10.1186/1479-5876-9-191 · Cited by 34 · see citing works
Yee, C., Lizee, G. A., & Schueneman, A. J. (2015) · The Cancer Journal · doi:10.1097/ppo.0000000000000158 · Cited by 29 · cited 1× · see citing works
“These encouraging results demonstrate that T cell-based cancer therapies offer great promise in inducing complete responses in patients against several types of cancer (Maude et al., 2014; Yee et al., 2015).”
ResultYee, C., & Lizee, G. A. (2017) · The Cancer Journal · doi:10.1097/ppo.0000000000000255 · Cited by 14 · cited 1× · see citing works
“In addition, neoantigen vaccines and checkpoint blockade therapies using anti-programed cell death 1 (PD-1) and anti-PD-ligand 1 (PD-L1) have shown potent therapeutic effects in patients with advanced cancer (Chapuis et al., 2016b; Yee and Lizee, 2017; Boyiadzis et al., 2018; Yee, 2018; Riley et al., 2019).”
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The foundations of immune checkpoint blockade and the ipilimumab approval decennial
Korman, A. J., Garrett-Thomson, S. C., & Lönberg, N. (2021) · Nature Reviews Drug Discovery · doi:10.1038/s41573-021-00345-8 · Cited by 561 · see citing works
Immunosenescence: a key player in cancer development
Lian, J., Yue, Y., Yu, W., & Zhang, Y. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00986-z · Cited by 510 · see citing works
Self-citationResistance Mechanisms of Anti-PD1/PDL1 Therapy in Solid Tumors
Lei, Q., Wang, D., Sun, K., Wang, L., & Zhang, Y. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00672 · Cited by 414 · see citing works
Self-citationImmune evasion in cancer: mechanisms and cutting-edge therapeutic approaches
Tufail, M., Jiang, C., & Li, N. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02280-1 · Cited by 424 · see citing works
Bao, H., Cao, J., Chen, M., Min, C., Chen, W., Chen, X., Chen, Y., Chen, Y., Chen, Y., Chen, Z., et al. (2023) · Science China Life Sciences · doi:10.1007/s11427-023-2305-0 · Cited by 389 · see citing works
Self-citationTargeting memory T cell metabolism to improve immunity
Corrado, M., & Pearce, E. L. (2022) · Journal of Clinical Investigation · doi:10.1172/jci148546 · Cited by 234 · see citing works
Güven, D. C., Şahin, T. K., Erul, E., Rizzo, A., Ricci, A. D., Aksoy, S., & Yalçın, Ş. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.1039121 · Cited by 214 · see citing works
“These agents act by removing the immunosuppression created by the T-cell exhaustive checkpoints in the tumor microenvironment to aid the immune system in fighting tumors more efficiently (Waldman et al., 2020; Zhang et al., 2020).”
BackgroundStraathof, K. C. M., Flutter, B. R., Wallace, R., Jain, N., Loka, T., Depani, S., Wright, G., Thomas, S., Cheung, G. W.-K., Gileadi, T. E., et al. (2020) · Science Translational Medicine · doi:10.1126/scitranslmed.abd6169 · Cited by 202 · see citing works
“Similarly, at the tumor site, sustained antigenic stimulation may help to either drive an exhaustion phenotype of CAR-T cells (41, 42) or drive effector cells to activationinduced cell death (43, 44).”
BackgroundGold Nanoparticles: Construction for Drug Delivery and Application in Cancer Immunotherapy
Huang, H., Liu, R., Yang, J., Dai, J., Fan, S., Pi, J., Wei, Y., & Guo, X. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15071868 · Cited by 197 · see citing works
“This indicates that a sustained immune effect can be generated while killing tumour cells [262].”
BackgroundTian, H., Wang, G., Sang, W., Xie, L., Zhang, Z., Li, W., Yan, J., Tian, Y., Li, J., Li, B., et al. (2022) · Nano Today · doi:10.1016/j.nantod.2022.101405 · Cited by 165 · see citing works
Self-citationAlnefaie, A., Albogami, S. M., Asiri, Y. A., Ahmad, T., Alotaibi, S. S., Al-Sanea, M. M., & Althobaiti, H. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.797440 · Cited by 153 · see citing works
“Different factors have been identified that play several roles in T-cell exhaustion; the intrinsic factors relate to transcription, epigenetic, and metabolic factors, whereas the extrinsic factors include extracellular and cytokine interactions that create the TME and the immunosuppressive network (Maimela et al., 201…”
BackgroundThe current state and future of T-cell exhaustion research
Jenkins, E. M., Whitehead, T., Fellermeyer, M., Davis, S. J., & Sharma, S. (2023) · Oxford Open Immunology · doi:10.1093/oxfimm/iqad006 · Cited by 136 · see citing works
“For example, Tregs, MDSCs and TAMs are commonly found in tumours and all have been implicated in helping drive T-cell exhaustion [132].”
BackgroundBigos, K. J. A., Quiles, C. G., Lunj, S., Smith, D. J., Krause, M., Troost, E. G. C., West, C., Hoskin, P., & Choudhury, A. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1331355 · Cited by 142 · see citing works
“T cells (CD8+ and CD4+) are an important component of the adaptive immune system and play a key role in eliminating tumour cells via various cytotoxic activities (210, 211).”
BackgroundZou, Y., Ruan, S., Jin, L., Chen, Z., Han, H., Zhang, Y., Jian, Z., Lin, Y., Shi, N., & Jin, H. (2020) · Medical Science Monitor · doi:10.12659/msm.925289 · Cited by 134 · see citing works
Self-citationPapavassiliou, A. G., & Musti, A. M. (2020) · Cells · doi:10.3390/cells9112470 · Cited by 122 · see citing works
Improving CAR T-Cell Persistence
Pietrobon, V., Todd, L. A., Goswami, A., Stefanson, O., Yang, Z., & Marincola, F. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910828 · Cited by 118 · see citing works
Annexin A1 as a Regulator of Immune Response in Cancer
Araújo, T. G., Mota, S. T. S., Ferreira, H. S. V., Ribeiro, M. A., Goulart, L. R., & Vecchi, L. (2021) · Cells · doi:10.3390/cells10092245 · Cited by 114 · see citing works
Immune Regulatory Processes of the Tumor Microenvironment under Malignant Conditions
Pansy, K., Uhl, B., Krstić, J., Szmyra, M., Fechter, K., Santiso, A., Thüminger, L., Greinix, H., Kargl, J., Prochazka, K. T., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222413311 · Cited by 110 · see citing works
Dual Relationship Between Stromal Cells and Immune Cells in the Tumor Microenvironment
Mun, J.-Y., Leem, S., Lee, J. H., & Kim, H. S. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.864739 · Cited by 105 · see citing works
Boyero, L., Sánchez-Gastaldo, A., Alonso, M. D., Noguera-Uclés, J. F., Molina‐Pinelo, S., & Bernabé, R. (2020) · Cancers · doi:10.3390/cancers12123729 · Cited by 104 · see citing works
The Age of Cyclic Dinucleotide Vaccine Adjuvants
Gogoi, H., Mansouri, S., & Jin, L. (2020) · Vaccines · doi:10.3390/vaccines8030453 · Cited by 101 · see citing works
The immune cell atlas of human neuroblastoma
Verhoeven, B. M., Mei, S., Olsen, T. K., Gustafsson, K. U., Valind, A., Lindström, A., Gisselsson, D., Fard, S. S., Hagerling, C., Kharchenko, P. V., et al. (2022) · Cell Reports Medicine · doi:10.1016/j.xcrm.2022.100657 · Cited by 100 · see citing works
Integrated Multi-Omics Landscape of Liver Metastases
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Bispecific antibodies in the treatment of multiple myeloma
Devasia, A. J., Chari, A., & Lancman, G. (2024) · Blood Cancer Journal · doi:10.1038/s41408-024-01139-y · Cited by 94 · see citing works
“T-cell exhaustion and dysfunction induced by continuous and persistent antigenic stimulation by BsAbs and other T cell directed therapies is another concern for failure of BsAb therapy [36, 110, 116, 126].”
BackgroundThe acidic tumour microenvironment: Manipulating the immune response to elicit escape
Worsley, C. M., Veale, R. B., & Mayne, E. S. (2022) · Human Immunology · doi:10.1016/j.humimm.2022.01.014 · Cited by 87 · see citing works
Point mutation in CD19 facilitates immune escape of B cell lymphoma from CAR-T cell therapy
Zhang, Z., Chen, X., Tian, Y., Li, F., Zhao, X., Liu, J., Yao, C., & Zhang, Y. (2020) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2020-001150 · Cited by 85 · see citing works
Self-citationNanomaterial-encapsulated STING agonists for immune modulation in cancer therapy
Chen, X., Xu, Z., Li, T., Thakur, A., Wen, Y., Zhang, K., Liu, Y., Liang, Q., Liu, W., Qin, J., et al. (2024) · Biomarker Research · doi:10.1186/s40364-023-00551-z · Cited by 83 · see citing works
“Furthermore, exhausted T cells (Tex) are characterized by dysfunction of effector functions that contribute to failures in immunotherapy [116].”
BackgroundTonic-signaling chimeric antigen receptors drive human regulatory T cell exhaustion
Lamarche, C., Ward‐Hartstonge, K. A., Tian, M., Lin, D. T. S., Huang, Q. B., Brown, A., Edwards, K., Novakovsky, G., Qi, C. N., Kobor, M. S., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2219086120 · Cited by 86 · see citing works
“Although viability was similar between the three groups, in accordance with exhausted T cells (19), TS-CAR Tregs were more apoptotic than controls (Fig.”
Nano Drug Delivery System for Tumor Immunotherapy: Next-Generation Therapeutics
Zhou, L., Zou, M., Xu, Y., Lin, P., Lei, C., & Xia, X. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.864301 · Cited by 76 · see citing works
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T‐Cell‐Derived Nanovesicles for Cancer Immunotherapy
Hong, J., Kang, M., Jung, M., Lee, Y. Y., Cho, Y., Kim, C., Song, S. Y., Park, C. G., Doh, J., & Kim, B. (2021) · Advanced Materials · doi:10.1002/adma.202101110 · Cited by 75 · see citing works
Sequential immunotherapy: towards cures for autoimmunity
Ramírez‐Valle, F., Maranville, J., Roy, S., & Plenge, R. M. (2024) · Nature Reviews Drug Discovery · doi:10.1038/s41573-024-00959-8 · Cited by 80 · see citing works
Evaluation of the Role of the Immune System Response After Minibeam Radiation Therapy
Bertho, A., Iturri, L., Brisebard, É., Juchaux, M., Gilbert, C., Ortiz, R., Sebrié, C., Jourdain, L., Lamirault, C., Ramasamy, G., et al. (2022) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2022.08.011 · Cited by 72 · see citing works
Dynamic chromatin regulatory landscape of human CAR T cell exhaustion
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Biomarkers for prediction of CAR T therapy outcomes: current and future perspectives
Sršen, L., Janžič, L., Ihan, A., & Kopitar, A. N. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1378944 · Cited by 72 · see citing works
“The dysregulation of metabolic pathways and the imbalance of metabolites can result in the production of ROS, causing further damage to immune cells and tissues, inhibiting the antitumor effect of T lymphocytes and CAR T cells, and promoting tumor growth (95, 172).”
BackgroundExhausted T cells and epigenetic status
Zeng, Z., Wei, F., & Ren, X. (2020) · Cancer Biology and Medicine · doi:10.20892/j.issn.2095-3941.2020.0338 · Cited by 70 · see citing works
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Mechanisms of Immune Evasion in Acute Lymphoblastic Leukemia
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Shao, S., Miao, H., & Ma, W. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1295684 · Cited by 66 · see citing works
“This low-oxygen condition intensi fi es the interactions between TAMs and other TME cells emphasizing the pivotal roles TAMs play, for instance, regulating T-cell functions (87, 88).”
BackgroundUnraveling exhaustion in adaptive and conventional NK cells
Merino, A. M., Kim, H., Miller, J. S., & Cichocki, F. M. (2020) · Journal of Leukocyte Biology · doi:10.1002/jlb.4mr0620-091r · Cited by 65 · see citing works
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Taurine enhances the antitumor efficacy of PD-1 antibody by boosting CD8+ T cell function
Yü, P., Shan, J., Liu, Y., Liu, F., Wang, L., Liu, Z., Li, J., Yue, D., Wang, L., Chen, X., et al. (2022) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-022-03308-z · Cited by 59 · see citing works
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Nano-immunotherapy for each stage of cancer cellular immunity: which, why, and what?
Zuo, S., Song, J., Zhang, J., He, Z., Sun, B., & Sun, J. (2021) · Theranostics · doi:10.7150/thno.59953 · Cited by 56 · see citing works
CXCL9-modified CAR T cells improve immune cell infiltration and antitumor efficacy
Tian, Y., Wen, C., Zhang, Z., Liu, Y., Li, F., Zhao, Q., Yao, C., Ni, K., Yang, S., & Zhang, Y. (2022) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-022-03193-6 · Cited by 56 · see citing works
Self-citationAhluwalia, P. K., Ahluwalia, M., Mondal, A. K., Sahajpal, N., Kota, V. K., Rojiani, M. V., Rojiani, A. M., & Kolhe, R. B. (2021) · Cancers · doi:10.3390/cancers13010155 · Cited by 52 · see citing works
Park, J. A., Wang, L., & Cheung, N. V. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01156-5 · Cited by 50 · see citing works
Augmenting the Effectiveness of CAR-T Cells by Enhanced Self-Delivery of PD-1-Neutralizing scFv
Yü, P., Li, F., Nan, S., Zhang, D., Shi, X., Shan, J., & Zhang, Y. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00803 · Cited by 51 · see citing works
“Nevertheless, CAR-T cells demonstrate very limited benefits to date in solid tumors (Li et al., 2018; Martinez and Moon, 2019; Yang et al., 2019; Zhang et al., 2020).”
BackgroundSelf-citationAzeez, S. S., Yashooa, R. K., Smail, S. W., Salihi, A. B., Ali, A. S., Mamand, S., & Janson, C. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02386-8 · Cited by 57 · see citing works
“Cytokines are crucial in driving T-cell exhaustion, negatively impacting their anti-tumour response [195].”
Monteran, L., Ershaid, N., Scharff, Y., Zoabi, Y., Sanalla, T., Ding, Y., Pavlovsky, A., Zait, Y., Langer, M., Caller, T., et al. (2024) · Cancer Discovery · doi:10.1158/2159-8290.cd-23-0762 · Cited by 54 · see citing works
Zhang, Z., Liu, J., Zhang, C., Li, F., Li, L., Wang, D., Chand, D., Guan, F., Zang, X., & Zhang, Y. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00280 · Cited by 47 · see citing works
“In one mechanism of tumor evasion from the immune system, tumor cells express coinhibitory ligands that result in T cell exhaustion and blunt the immune response (Chen et al., 2018; Zhang et al., 2020).”
BackgroundSelf-citationTaylor, J., Gandhi, A., Gray, E. S., & Zaenker, P. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.991433 · Cited by 47 · see citing works
Sadhukhan, P., Feng, M., Illingworth, E. J., Sloma, I., Ooki, A., Matoso, A., Sidransky, D., Johnson, B. A., Marchionni, L., Sillé, F. C. M., et al. (2024) · Journal of Clinical Investigation · doi:10.1172/jci171164 · Cited by 47 · see citing works
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Regulation of post-translational modification of PD-L1 and advances in tumor immunotherapy
Feng, C., Zhang, L., Chang, X., Qin, D., & Zhang, T. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1230135 · Cited by 45 · see citing works
Exhausted T cells hijacking the cancer-immunity cycle: Assets and liabilities
Brunell, A. E., Lahesmaa, R., Autio, A. K., & Thotakura, A. K. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1151632 · Cited by 42 · see citing works
Racacho, K. J., Shiau, Y., Villa, R., Mahri, S., Tang, M., Lin, T., & Li, Y. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1621812 · Cited by 54 · see citing works
“T cell exhaustion can also occur, leading to immune cell dysfunction and an inability to effectively target the tumor (169).”
Hydrogels to engineer tumor microenvironments in vitro
Fernando, K., Kwang, L. G., Lim, J. T. C., & Fong, E. L. S. (2021) · Biomaterials Science · doi:10.1039/d0bm01943g · Cited by 43 · see citing works
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“…interest in understanding the differentiation of Tpex cells for immunotherapy use in cancer and chronically infected patients; Tpex cells provide the effector T cell proliferative burst after immune checkpoint blockade (ICB) and may have therapeutic predictive value in patients 10,15,16,63,64 .”
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Jancewicz, I., Szarkowska, J., Konopiński, R., Stachowiak, M., Swiatek, M., Błachnio, K., Kubala, S., Oksinska, P., Cwiek, P., Rusetska, N., et al. (2021) · Cancers · doi:10.3390/cancers13164148 · Cited by 42 · see citing works
Nanoparticle Enhancement of Natural Killer (NK) Cell-Based Immunotherapy
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Wang, K., & Zhou, H. (2020) · Drug Development Research · doi:10.1002/ddr.21765 · Cited by 40 · see citing works
“Multiple immune checkpoints are involved in tumor evasion (Zhang et al., 2020).”
BackgroundNelde, A., Maringer, Y., Bilich, T., Salih, H. R., Roerden, M., Heitmann, J. S., Marcu, A., Bauer, J., Neidert, M. C., Denzlinger, C., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.705974 · Cited by 37 · see citing works
Mishra, V., Tripathi, V., Yadav, P., & Singh, M. P. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.123617 · Cited by 39 · see citing works
The Interplay between T Cells and Cancer: The Basis of Immunotherapy
Chen, C., Liu, X., Chang, C., Wang, H. Y., & Wang, R. (2023) · Genes · doi:10.3390/genes14051008 · Cited by 39 · see citing works
The Force is Strong with This Epigenome: Chromatin Structure and Mechanobiology
Hsia, C.-R., Melters, D. P., & Dalal, Y. (2023) · Journal of Molecular Biology · doi:10.1016/j.jmb.2023.168019 · Cited by 40 · see citing works
CAR-T cells, from principle to clinical applications
Bourbon, E., Ghesquières, H., & Bachy, E. (2021) · Bulletin du Cancer · doi:10.1016/j.bulcan.2021.02.017 · Cited by 40 · see citing works
Mitoribosomal defects aggravate liver cancer via aberrant glycolytic flux and T cell exhaustion
Song, B.-S., Moon, J. S., Tian, J., Lee, H. Y., Sim, B. C., Kim, S., Kang, S., Kim, J. T., Nga, H. T., Benfeitas, R., et al. (2022) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2021-004337 · Cited by 39 · see citing works
“In the light of mitochondrial dysfunction in HCC, expression profiles of mitoribosomal genes can be considered as critical biomarkers of disease severity and progression in HCC patients.”
Ao, Z., Wu, Z., Cai, H., Hu, L., Li, X., Kaurich, C., Chang, J., Gu, M., Liang Cheng, C., Lü, X., et al. (2022) · Advanced Science · doi:10.1002/advs.202201478 · Cited by 40 · see citing works
Self-assembling peptides as immunomodulatory biomaterials
Hernández, A., Hartgerink, J. D., & Young, S. W. (2023) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2023.1139782 · Cited by 39 · see citing works
“A faster release of anti-TNF-α was achieved due to protein diffusion through the KLD2R hydrogel, while the slower release of HGF was due to a combination of heparin-binding affinity and molecular diffusion.”
BackgroundInfluentialWang, S., Kuai, Y., Lin, S., Li, L., Gu, Q., Zhang, X., Li, X., He, Y., Chen, S., Xia, X., et al. (2023) · BMC Medicine · doi:10.1186/s12916-023-02791-0 · Cited by 37 · see citing works
Self-citationFluorogenic Granzyme A Substrates Enable Real‐Time Imaging of Adaptive Immune Cell Activity
Cheng, Z., Thompson, E. J., Mendive‐Tapia, L., Scott, J. I., Benson, S., Kitamura, T., Senan‐Salinas, A., Samarakoon, Y., Roberts, E. W., Arias, M. A., et al. (2022) · Angewandte Chemie International Edition · doi:10.1002/anie.202216142 · Cited by 37 · see citing works
Shen, C., Zhang, Z., Tian, Y.-G., Li, F., Zhou, L., Jiang, W.-Y., Yang, L., Zhang, B., Wang, L.-P., & Zhang, Y. (2021) · BMC Medicine · doi:10.1186/s12916-021-02161-8 · Cited by 33 · see citing works
Self-citationReprogramming the tumor microenvironment with biotechnology
Kim, M., Lee, N. K., Wang, C. J., Lim, J., Byun, M. J., Kim, T. P., Park, W., Park, D.-H., Kim, S.-N., & Park, C. G. (2023) · Biomaterials Research · doi:10.1186/s40824-023-00343-4 · Cited by 37 · see citing works
“The upregulation of immune checkpoints and conversion into transcriptional and metabolic molecules are considered T cell dysfunction [90].”
BackgroundShen, C., Liu, C., Zhang, Z., Yü, P., Shao, J., Tian, Y., Yu, W., Qin, G., Liu, S., Wang, L., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.680055 · Cited by 35 · see citing works
Self-citationSaliba, J., Coutaud, B., Makhani, K., Roth, N. E., Jackson, J., Park, J. Y., Gagnon, N., Costa, P., Jeyakumar, T., Bury, M., et al. (2022) · Oncogene · doi:10.1038/s41388-022-02192-2 · Cited by 35 · see citing works
“This is of interest as tumors infiltrated with exhausted T cells are considered hot tumors that are responsive to immune checkpoint inhibitor drugs aimed at reactivating the infiltrated T cells [57].”
BackgroundExploring immune checkpoint inhibitors: Focus on PD-1/PD-L1 axis and beyond
Aden, D., Zaheer, S., Sureka, N., Trisal, M., Chaurasia, J. K., & Zaheer, S. (2025) · Pathology - Research and Practice · doi:10.1016/j.prp.2025.155864 · Cited by 37 · see citing works
Brauneck, F., Haag, F., Woost, R., Wildner, N. H., Tolosa, E., Rissiek, A., Vohwinkel, G., Wellbrock, J., Bokemeyer, C., Wiesch, J. S. Z., et al. (2021) · OncoImmunology · doi:10.1080/2162402x.2021.1930391 · Cited by 34 · see citing works
“One of the most important features of T-cell dysfunction seem to be the co-expression of multiple inhibitory receptors.(40) We observed increased frequencies of the PD-1TIGITCD73CD8and CD39TIGITCD73CD8 T-cell subsets in PB and BM from patients with newly diagnosed and relapsed AML.”
BackgroundAnti‐tumour potential of PD‐L1 / PD ‐1 post‐translational modifications
Zhou, S., Zhu, J., Xu, J., Gu, B., Zhao, Q., Luo, C., Gao, Z., Chin, Y. E., & Cheng, X. (2022) · Immunology · doi:10.1111/imm.13573 · Cited by 36 · see citing works
“Binding with their ligands, they initiate negative co-stimulation signals during antigen presentation to T cells, thus preventing over-activation [6, 7].”
Backgroundvan Elsas, M. J., Labrie, C., Etzerodt, A., Charoentong, P., Thans, J. J. C. V. S., van Hall, T., & van der Burg, S. H. (2023) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2022-006433 · Cited by 36 · see citing works
Ma, R., Zhou, X., Zhai, X., Wang, C., Hu, R., Chen, Y., Shi, L., Fang, X., Liao, Y., Ma, L., et al. (2024) · Cell Proliferation · doi:10.1111/cpr.13591 · Cited by 33 · see citing works
“9,10,25 Additionally, gene sets associated with senescence, including ribosome and histone genes, showed no significant differences between HAGC and NAGC, although there was a slight reduction compared to healthy controls (Figure 4D and Supplementary Figure S4C).”
ResultTiragolumab and TIGIT: pioneering the next era of cancer immunotherapy
Ghasemi, K. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1568664 · Cited by 33 · see citing works
Peptide-Based Vaccines for Hepatocellular Carcinoma: A Review of Recent Advances
Charneau, J., Suzuki, T., Shimomura, M., Fujinami, N., & Nakatsura, T. (2021) · Journal of Hepatocellular Carcinoma · doi:10.2147/jhc.s291558 · Cited by 33 · see citing works
Immune Checkpoint Inhibitor Associated Myocarditis and Cardiomyopathy: A Translational Review
Wang, D., Bauersachs, J. K., & Berliner, D. (2023) · Biology · doi:10.3390/biology12030472 · Cited by 34 · see citing works
Co-Expression of miR155 or LSD1 shRNA Increases the Anti-Tumor Functions of CD19 CAR-T Cells
Zhang, J., Zhu, J., Zheng, G., Wang, Q., Li, X., Feng, Y., Shang, F., He, S., Jiang, Q., Shi, B., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2021.811364 · Cited by 34 · see citing works
Repolarization of Tumor-Infiltrating Myeloid Cells for Augmentation of CAR T Cell Therapies
Luo, W., Napoleon, J. V., Zhang, F., Lee, Y. G., Wang, B., Putt, K. S., & Low, P. S. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.816761 · Cited by 32 · see citing works
Therapy-induced shaping of the glioblastoma microenvironment: Macrophages at play
Erbani, J. M., Boon, M., & Akkari, L. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.05.003 · Cited by 32 · see citing works
B Cells in Breast Cancer Pathology
Li, M., Quintana, Á., Alberts, E., Hung, M. S., Boulat, V., Martı́, M., & Grigoriadis, A. E. (2023) · Cancers · doi:10.3390/cancers15051517 · Cited by 34 · see citing works
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CD8+ T Cells in SARS-CoV-2 Induced Disease and Cancer—Clinical Perspectives
Mortezaee, K., & Majidpoor, J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.864298 · Cited by 34 · see citing works
Strategies to overcome myeloid cell induced immune suppression in the tumor microenvironment
Cao, J. H., Chow, L., & DOW, S. W. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1116016 · Cited by 32 · see citing works
Bi, C., Patel, J. S., & Liang, S. H. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c02151 · Cited by 30 · see citing works
Shao, J., Hou, L., Liu, J., Liu, Y., Ning, J., Zhao, Q., & Zhang, Y. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.661357 · Cited by 30 · see citing works
Self-citationO'Reilly, M. A., Wilson, W., Burns, D., Kühnl, A., Seymour, F., Uttenthal, B., Besley, C., Alajangi, R., Creasey, T., Paneesha, S., et al. (2024) · HemaSphere · doi:10.1002/hem3.87 · Cited by 29 · see citing works
“35 Although, the manufacture of brexu ‐ cel encompasses a T ‐ cell selection step to remove contaminating cells from the harvest material, it is conceivable that circulating MCL cells in the peripheral blood, namely the TME, may contribute to inherent T ‐ cell dysfunction and failure of expansion…”
BackgroundBrownlie, D., von Kries, A., Valenzano, G., Wild, N., Yilmaz, E., Säfholm, J., Al‐Ameri, M., Alici, E., Ljunggren, H., Schliemann, I., et al. (2023) · OncoImmunology · doi:10.1080/2162402x.2023.2233402 · Cited by 29 · see citing works
“While conventional intratumoral NK cell and T cell subsets are considered hypofunctional 19,20 , our results suggest that trNK cells are tumor target cell-responsive.”
Antibody Responses to COVID-19 Vaccination in Cancer: A Systematic Review
Güven, D. C., Şahin, T. K., Kılıçkap, S., & Uckun, F. M. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.759108 · Cited by 27 · see citing works
Obesity and adipose tissue impact on T-cell response and cancer immune checkpoint blockade therapy
Pasquarelli-do-Nascimento, G., Machado, S. A., de Carvalho, J. M. A., & Magalhães, K. G. (2022) · Immunotherapy Advances · doi:10.1093/immadv/ltac015 · Cited by 28 · see citing works
“The obese phenotype copes with T lymphocyte dysfunction, a state characterized by a hyporesponsive profile, associated with loss of effector, proliferative capacity, and reduced production of cytokines, TNF-α and IFN-γ, in conditions that can be classified as anergy or exhaustion [123].”
Background
- Authors
- Zhang, Z., Liu, S., Zhang, B., Qiao, L., Zhang, Y., & Zhang, Y.
- Affiliations
- First Affiliated Hospital of Zhengzhou University (CN)
- Northwestern University (US)
- Loyola University Chicago (US)
- Venue
- Frontiers in Cell and Developmental Biology
- Publisher
- Frontiers Media SA
- Published
- 2020-02-11
- Volume
- 8
- Pages
- 17-17
- ISSN
- 2296-634X (ISSN-L)
- PMC
- PMC7027373
- OpenAlex
- W3006138994
- Cited by
- 385
- References
- 120
- Citations by year
- 2026: 39 · 2025: 52 · 2024: 70 · 2023: 64 · 2022: 65 · 2021: 60 · 2020: 34 · 2019: 1
- FWCI
- 5.99
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Cell and Developmental Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (U1804281, 81771781, 81702810, 81773060)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- T cell dysfunction, T cell exhaustion, cancer immunotherapy, tumor microenvironment, inhibitory receptors, antitumor immunity, immunotherapy resistance
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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