Cited by 388Cancer Immunotherapy and BiomarkersT-cell and B-cell ImmunologyImmunotherapy and Immune Responses

The DOI matches its Crossref record; 138 of the 140 references it cites were found in a registry or an index.

Exhaustion and senescence: two crucial dysfunctional states of T cells in the tumor microenvironment

Open access

Zhao, Yangjing, Shao, Qixiang, Peng, Guangyong·2020·Cellular & Molecular Immunology

DOI 10.1038/s41423-019-0344-8PMC PMC6952436

Open this paper in CoChat — free account

Abstract

The failure of a massive influx of tumor-infiltrating T lymphocytes to eradicate tumor cells in the tumor microenvironment is mainly due to the dysfunction of T cells hyporesponsive to tumors. T-cell exhaustion and senescence induced by malignant tumors are two important dysfunctional states that coexist in cancer patients, hindering effective antitumor immunity and immunotherapy and sustaining the suppressive tumor microenvironment. Although exhausted and senescent T cells share a similar dysfunctional role in antitumor immunity, they are distinctly different in terms of generation, development, and metabolic and molecular regulation during tumor progression. Here, we discuss the unique phenotypic and functional characteristics of these two types of dysfunctional T cells and their roles in tumor development and progression. In addition, we further discuss the potential molecular and metabolic signaling pathways responsible for the control of T-cell exhaustion and senescence in the suppressive tumor microenvironment. Understanding these critical and fundamental features should facilitate rethinking the unresponsiveness to current immunotherapies in clinical patients and lead to further development of novel and effective strategies that target different types of dysfunctional T cells to enhance cancer immunotherapy.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1038/s41423-019-0344-8

Cites

138 of 138 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
The blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838
A biomarker that identifies senescent human cells in culture and in aging skin in vivo.
Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., & Pereira-Smith, O. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.20.9363 · Cited by 7,477
The limited in vitro lifetime of human diploid cell strains
Hayflick, L. (1965) · Experimental Cell Research · doi:10.1016/0014-4827(65)90211-9 · Cited by 5,876
The senescence-associated secretory phenotype: the dark side of tumor suppression
Coppé, J.-P., Desprez, P.-Y., Krtolica, A., & Campisi, J. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-121808-102144 · Cited by 5,206
Molecular and cellular insights into T cell exhaustion
Wherry, E. J., & Kurachi, M. (2015) · Nature Reviews Immunology · doi:10.1038/nri3862 · Cited by 4,652
Cellular senescence: when bad things happen to good cells
Campisi, J., & d'Adda di Fagagna, F. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2233 · Cited by 4,441
Immune Checkpoint Blockade: A Common Denominator Approach to Cancer Therapy
Topalian, S. L., Drake, C. G., & Pardoll, D. M. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.03.001 · Cited by 4,229
T cell exhaustion
Wherry, E. J. (2011) · Nature Immunology · doi:10.1038/ni.2035 · Cited by 4,062
Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression
Chang, C.-H., Qiu, J., O’Sullivan, D., Buck, M. D., Noguchi, T., Curtis, J. D., Chen, Q., Gindin, M., Gubin, M. M., van der Windt, G. J. W., et al. (2015) · Cell · doi:10.1016/j.cell.2015.08.016 · Cited by 3,331

Show all 140 references

Research works printed but not linked: 2

Fourcade, J. et al. Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen-specific CD8(+) T cell dysfunction in melanoma patients. J. Exp. Med. 207, 2175–2186 (2010). · DOI · Paper page
Brenchley, J. M. et al. Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells. Blood 101, 2711–2720 (2003). · DOI · Paper page

Sorted by citations

Items 101–200 of 388

Advancements in Personalized CAR-T Therapy: Comprehensive Overview of Biomarkers and Therapeutic Targets in Hematological Malignancies
Olejarz, W., Sadowski, K. A., Szulczyk, D., & Basak, G. W. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25147743 · Cited by 26
T cell exhaustion and senescence for ovarian cancer immunotherapy
Zhao, J., Wang, Z., Tian, Y., Ning, J., & Ye, H. (2024) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2024.07.001 · Cited by 26
Senescent Tumor CD8+ T Cells: Mechanisms of Induction and Challenges to Immunotherapy
Liu, W., Stachura, P., Xu, H. C., Bhatia, S., Borkhardt, A., Lang, P. A., & Pandyra, A. A. (2020) · Cancers · doi:10.3390/cancers12102828 · Cited by 27
Senescent Tumor Cells in the Peritoneal Carcinomatosis Drive Immunosenescence in the Tumor Microenvironment
Braumüller, H., Mauerer, B., Berlin, C., Plundrich, D., Marbach, P., Cauchy, P., Laessle, C., Biesel, E. A., Holzner, P. A., & Kesselring, R. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.908449 · Cited by 24
Clinical Value of the PD-1/PD-L1/PD-L2 Pathway in Patients Suffering from Endometriosis
Suszczyk, D., Skiba, W., Zardzewiały, W., Pawłowska, A., Włodarczyk, K., Polak, G., Tarkowski, R., & Wertel, I. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911607 · Cited by 26
PBRM1 mutation as a predictive biomarker for immunotherapy in multiple cancers
Dai, J., Cui, Y., Xiao, L., Xu, J., Li, J., Chen, Y., Zhang, E., & Guo, R. (2023) · Frontiers in Genetics · doi:10.3389/fgene.2022.1066347 · Cited by 26
Reprogramming cellular senescence and aging clocks for advanced cancer immunotherapy
Yang, H., Liu, D., Qiu, L., Wang, R., Zhang, C., Yu, D., Zhong, Q., Yuki, N., Song, Z., Zhu, Τ., et al. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02459-8 · Cited by 30
Tumor-derived extracellular vesicles in melanoma immune response and immunotherapy
Zhou, Q., Yan, Y., Li, Y., Fu, H., Lu, D., Li, Z., Wang, Y., Wang, J., Zhu, H., Ren, J., et al. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113790 · Cited by 23
The Impact of Microgravity on Immunological States.
Hicks, J., Olson, M., Mitchell, C., Juran, C. M., & Paul, A. M. (2023) · PubMed Central · doi:10.4049/immunohorizons.2200063 · Cited by 30
p21 Prevents the Exhaustion of CD4+ T Cells Within the Antitumor Immune Response Against Colorectal Cancer
Thoma, O., Naschberger, E., Kubánková, M., Larafa, I., Kramer, V., Menchicchi, B., Merkel, S., Britzen‐Laurent, N., Jefremow, A., Grützmann, R., et al. (2023) · Gastroenterology · doi:10.1053/j.gastro.2023.09.017 · Cited by 22
The Emerging Role of Schwann Cells in the Tumor Immune Microenvironment and Its Potential Clinical Application
Zhang, S., Chen, J., Cheng, F., & Fang, Z. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252413722 · Cited by 23
Unravelling the Connection Between Energy Metabolism and Immune Senescence/Exhaustion in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Campenhout, J. V., Buntinx, Y., Xiong, H.-Y., Wyns, A., Polli, A., Nijs, J., Aerts, J. L., Laeremans, T., & Hendrix, J. (2025) · Biomolecules · doi:10.3390/biom15030357 · Cited by 22
ADRB3 induces mobilization and inhibits differentiation of both breast cancer cells and myeloid-derived suppressor cells
Zhou, Z., Zhan, J., Luo, Q., Hou, X., Wang, S., Xiao, D., Xie, Z., Liang, H., Lin, S., & Zheng, M. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04603-4 · Cited by 22
Immunosenescence and age-related immune cells: causes of age-related diseases
Kim, N., Sim, S.-J., Han, H.-G., Yoon, J.-H., & Han, Y. (2024) · Archives of Pharmacal Research · doi:10.1007/s12272-024-01529-7 · Cited by 22
Integration of multi-omics data reveals a novel hybrid breast cancer subtype and its biomarkers
Wang, Z., Li, X., Wen, X.-L., Wang, N., Guo, Y., Xu, Z., Fu, S.-H., Xiong, F.-F., Bai, J., Gao, X., et al. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1130092 · Cited by 22
Natural Killer Cells: A Promising Kit in the Adoptive Cell Therapy Toolbox
Xiao, J., Zhang, T., Gao, F., Zhou, Z., Shu, G., Zou, Y., & Yin, G. (2022) · Cancers · doi:10.3390/cancers14225657 · Cited by 19
The cell cycle regulator p16 promotes tumor infiltrated CD8+ T cell exhaustion and apoptosis
Zhang, X., Wang, J., Tang, K., Yang, Y., Liu, X., Yuan, S., Guo, F., Zhang, L., & Ma, K. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06721-7 · Cited by 21
Tumor glucose metabolism and the T cell glycocalyx: implication for T cell function
Schuurmans, F., Wagemans, K. E., Adema, G. J., & Cornelissen, L. A. M. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1409238 · Cited by 20
Mitochondrial Transplantation Promotes Protective Effector and Memory CD4 + T Cell Response During Mycobacterium Tuberculosis Infection and Diminishes Exhaustion and Senescence in Elderly CD4 + T cells
Headley, C. A., Gautam, S., Olmo-Fontánez, A. M., Garcia‐Vilanova, A., Dwivedi, V., Schami, A., Weintraub, S. T., Tsao, P. S., Torrelles, J. B., & Turner, J. (2024) · Advanced Science · doi:10.1002/advs.202401077 · Cited by 18
Immunotherapeutic approaches in Hepatocellular carcinoma: Building blocks of hope in near future
Minaei, N., Ramezankhani, R., Tamimi, A., Piryaei, A., Zarrabi, A., Aref, A. R., Mostafavi, E., & Vosough, M. (2022) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2022.151284 · Cited by 19
Implications of Senescent T Cells for Cancer Immunotherapy
Kasamatsu, T. (2023) · Cancers · doi:10.3390/cancers15245835 · Cited by 20
SHMT2 regulates CD8+ T cell senescence via the reactive oxygen species axis in HIV-1 infected patients on antiretroviral therapy
Zhang, Q.-S., Wang, J.-N., Yang, T.-L., Li, S., Li, J., Liu, D.-N., Shang, H., & Zhang, Z. (2025) · EBioMedicine · doi:10.1016/j.ebiom.2024.105533 · Cited by 19
T-cell dysfunction in natural killer/T-cell lymphoma
Feng, X., Meng, M., Li, H., Gao, Y., Song, W., Di, R., Li, Z., Zhang, X., & Zhang, M. (2023) · OncoImmunology · doi:10.1080/2162402x.2023.2212532 · Cited by 18
Optimizing CD8+ T cell-based immunotherapy via metabolic interventions: a comprehensive review of intrinsic and extrinsic modulators
Zhou, Z., Zheng, J., Lu, Y., Mai, Z., Lin, Y., Lin, P., Zheng, Y., Chen, X., Xu, R., Zhao, X., et al. (2024) · Experimental Hematology and Oncology · doi:10.1186/s40164-024-00575-7 · Cited by 19
Deregulated Expression of Immune Checkpoints on Circulating CD4 T Cells May Complicate Clinical Outcome and Response to Treatment with Checkpoint Inhibitors in Multiple Myeloma Patients
de Nałęcz, A. K., Ciszak, L., Usnarska‐Zubkiewicz, L., Frydecka, I., Pawlak, E., Szmyrka−Kaczmarek, M., & Kosmaczewska, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179298 · Cited by 18
A Forgotten Corner in Cancer Immunotherapy: The Role of Lipids
Yu, Y., Gao, L., Wang, Y., Xu, B., Maswikiti, E. P., Li, H., Peng, Z., Tao, P., Xiang, L., Gu, B., et al. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.751086 · Cited by 18
Aging-associated immune system changes in multiple myeloma: The dark side of the moon.
Visram, A., & Kourelis, T. (2021) · Cancer Treatment and Research Communications · doi:10.1016/j.ctarc.2021.100494 · Cited by 20
Seminoma subtypes differ in the organization and functional state of the immune microenvironment
Savelyeva, A., & Medvedev, K. E. (2023) · 3 Biotech · doi:10.1007/s13205-023-03530-1 · Cited by 17
Current and potential roles of immuno-PET/-SPECT in CAR T-cell therapy
Mulgaonkar, A., Udayakumar, D., Yang, Y., Harris, S. F., Öz, O. K., Geethakumari, P. R., & Sun, X. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1199146 · Cited by 18
Immune Diseases Associated with Aging: Molecular Mechanisms and Treatment Strategies
Kim, M. E., & Lee, J. S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242115584 · Cited by 20
The inter-link of ageing, cancer and immunity: findings from real-world retrospective study
Fu, X., Qin, P., Li, F., Zhu, H., You, H., Zhang, Y., Xu, B., Li, T., Zhang, F., Han, L., et al. (2023) · Immunity & Ageing · doi:10.1186/s12979-023-00399-9 · Cited by 19
Fungi, immunosenescence and cancer
Xu, B., Luo, Z., Niu, X., Li, Z., Lu, Y., & Li, J. (2025) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2025.01.002 · Cited by 17
Targeting amino acid metabolism to inhibit gastric cancer progression and promote anti-tumor immunity: a review
Jiang, Y., Qing, T., Qiao, X., Yang, Y., Chen, P., Han, M., Dong, K., Zhang, W., Xu, M., Wang, D., et al. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1508730 · Cited by 18
NK Cell Senescence in Cancer: From Molecular Mechanisms to Therapeutic Opportunities
Qiu, Z., Li, Z., Zhang, C., Zhao, Q., Liu, Z., Cheng, Q., Zhang, J., Lin, A., & Luo, P. (2025) · Aging and Disease · doi:10.14336/ad.2025.0053 · Cited by 18
LAMA4+ CD90+ eCAFs provide immunosuppressive microenvironment for liver cancer through induction of CD8+ T cell senescence
Zhang, J., Li, Z., Zhang, Q., Ma, W., Fan, W., Dong, J., Tian, J., Liao, H., Guo, J., Cao, Y., et al. (2025) · Cell Communication and Signaling · doi:10.1186/s12964-025-02162-7 · Cited by 17
Immune Checkpoints in Pediatric Solid Tumors: Targetable Pathways for Advanced Therapeutic Purposes
Cocco, C., Morandi, F., & Airoldi, I. (2021) · Cells · doi:10.3390/cells10040927 · Cited by 18
Epigenetic modulation of the tumor microenvironment in head and neck cancer: Challenges and opportunities
dos Santos, E. S., Wagner, V. P., Ramos, J. C., Lambert, D., CASTILHO, R. M., & Leme, A. F. P. (2021) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2021.103397 · Cited by 16
Interferon‑stimulated gene 15 promotes progression of endometrial carcinoma and weakens antitumor immune response
Zhao, X., Wang, J., Yaojie, Y., Zhang, M., Zhao, W., Zhang, H., & Zhao, L. (2022) · Oncology Reports · doi:10.3892/or.2022.8321 · Cited by 16
Neoadjuvant chemotherapy modulates exhaustion of T cells in breast cancer patients
Rodríguez, I. J., Bernal-Estévez, D. A., Llano-León, M., Bonilla, C., & Parra-López, C. (2023) · PLoS ONE · doi:10.1371/journal.pone.0280851 · Cited by 16
Age- and diet-instructed metabolic rewiring of the tumor–immune microenvironment
Plata-Gómez, A. B., & Ho, P. (2025) · The Journal of Experimental Medicine · doi:10.1084/jem.20241102 · Cited by 17
A Comprehensive Review of Long Non-Coding RNAs in the Cancer–Immunity Cycle: Mechanisms and Therapeutic Implications
Perez-Medina, M., Benito-Lopez, J. J., Aguilar‐Cázares, D., & López-González, J. S. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26104821 · Cited by 15
Next-generation T cell immunotherapy: overcoming exhaustion, senescence, and suppression
Li, G., Li, D., & Zhu, X. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1662145 · Cited by 17
Enhancing anti-tumor efficacy and immune memory by combining 3p-GPC-3 siRNA treatment with PD-1 blockade in hepatocellular carcinoma
Shao, L., Yu, X., Han, Q., Zhang, X., Lü, N., & Zhang, C. (2022) · OncoImmunology · doi:10.1080/2162402x.2021.2010894 · Cited by 16
Characterization of Antigen-Induced CD4+ T-Cell Senescence in Multiple Sclerosis
Ojer, P. T., Puthenparampil, M., Cruciani, C., Docampo, M. J., Martinꝉ, R., & Sospedra, M. (2022) · Frontiers in Neurology · doi:10.3389/fneur.2022.790884 · Cited by 15
Biallelic germline mutations in MAD1L1 induce a syndrome of aneuploidy with high tumor susceptibility
Villarroya‐Beltri, C., Osório, A., Torres-Ruiz, R., Gómez-Sánchez, D., Trakala, M., Sánchez-Belmonte, A., Mercadillo, F., Hurtado, B., Pitarch, B., Hernández‐Núñez, A., et al. (2022) · Science Advances · doi:10.1126/sciadv.abq5914 · Cited by 15
VLA-4 suppression by senescence signals regulates meningeal immunity and leptomeningeal metastasis
Li, J., Huang, D., Lei, B., Huang, J., Yang, L., Nie, M., Su, S., Zhao, Q., & Wang, Y. (2022) · eLife · doi:10.7554/elife.83272 · Cited by 15
Myeloid cells meet CD8+ T cell exhaustion in cancer: What, why and how
Zhai, Y., Liang, X., & Deng, M. (2024) · Chinese Journal of Cancer Research · doi:10.21147/j.issn.1000-9604.2024.06.04 · Cited by 14
Immune Aging, Immunosenescence, and Inflammaging: Implications for Vaccine Response in Older Adults
Falahi, S., Abdoli, A., & Kenarkoohi, A. (2025) · Health Science Reports · doi:10.1002/hsr2.71119 · Cited by 19
Cancer evolution: Special focus on the immune aspect of cancer
Hu, X., Chen, Z., Wang, Z., & Xiao, Q. (2022) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2022.05.006 · Cited by 14
Lipid metabolic remodeling delays senescence of T cells to potentiate their immunity against solid tumors
Xu, Y., Ding, L., Wu, M., Wang, X., Wang, L., Xu, Z., Xia, Y., Cao, Z., Zhang, Y., Song, R., et al. (2025) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2024-010403 · Cited by 16
Immune Checkpoints and the Immunology of Liver Fibrosis
Tsomidis, I., Voumvouraki, A., & Kouroumalis, E. (2025) · Livers · doi:10.3390/livers5010005 · Cited by 14
Role of Senescence in Tumorigenesis and Anticancer Therapy
Stoczyńska-Fidelus, E., Węgierska, M., Kierasińska, A., Ciunowicz, D., & Rieske, P. (2022) · Journal of Oncology · doi:10.1155/2022/5969536 · Cited by 15
Chimeric antigen receptor cell therapy: A revolutionary approach transforming cancer treatment to autoimmune disease therapy
Wen, R., Li, B., Wu, F., Mao, J., Azad, T., Wang, Y., Zhu, J., Zhou, X. Y., Xie, H., Qiu, X., et al. (2025) · Autoimmunity Reviews · doi:10.1016/j.autrev.2025.103859 · Cited by 14
Stromal senescence contributes to age-related increases in cancer
Ye, J., Melam, A., & Stewart, S. A. (2025) · Nature reviews. Cancer · doi:10.1038/s41568-025-00840-9 · Cited by 16
Lymphoma accelerates T cell and tissue aging
Hesterberg, R. S., Davis, J. T., Handoo, K. J., Elmarsafawi, A. G., Augello, A. C., Cheng, C., Atkins, R. M., Lee, D. H., Yang, C., Yao, J., et al. (2025) · Cancer Cell · doi:10.1016/j.ccell.2025.07.023 · Cited by 14
Uncovering the significance of expanded CD8+ large granular lymphocytes in inclusion body myositis: Insights into T cell phenotype and functional alterations, and disease severity
McLeish, E., Sooda, A., Slater, N., Kachigunda, B., Beer, K., Paramalingam, S., Lamont, P. J., Chopra, A., Mastaglia, F. L., Needham, M., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1153789 · Cited by 13
Hurdle or thruster: Glucose metabolism of T cells in anti-tumour immunity
Zhang, S., Zhang, X., Yang, H., Liang, T., & Bai, X. (2023) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2023.189022 · Cited by 14
Loss of CD96 Expression as a Marker of HIV-Specific CD8+ T-Cell Differentiation and Dysfunction
Bunet, R., Nayrac, M., Ramani, H., Sylla, M., Durand, M., Chartrand‐Lefebvre, C., Routy, J., LANDAY, A. L., Gauchat, J., Chomont, N., et al. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.673061 · Cited by 15
Inappropriate Expression of PD-1 and CTLA-4 Checkpoints in Myeloma Patients Is More Pronounced at Diagnosis: Implications for Time to Progression and Response to Therapeutic Checkpoint Inhibitors
Kulikowska de Nałęcz, A., Ciszak, L., Usnarska-Zubkiewicz, L., Pawlak, E., Frydecka, I., Szmyrka, M., & Kosmaczewska, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065730 · Cited by 13
The Breast Tumor Microenvironment: Could Silicone Breast Implant Elicit Breast Carcinoma?
Fleury, E. D. F. C., Nimir, C., & D’Alessandro, G. S. (2021) · Breast Cancer Targets and Therapy · doi:10.2147/bctt.s294166 · Cited by 13
Anti‐thymocyte globulin‐mediated immunosenescent alterations of T cells in kidney transplant patients
Lee, G. H., Lee, J. Y., Jang, J., Kang, Y. J., Choi, S. A., Kim, H. C., Park, S., Kim, M. S., & Lee, W. (2022) · Clinical & Translational Immunology · doi:10.1002/cti2.1431 · Cited by 12
Peripheral immune cell response to stimulation stratifies Parkinson’s disease progression from prodromal to clinical stages
Mark, J. R., Titus, A. M., Staley, H. A., Alvarez, S. D., Mahn, S., McFarland, N. R., Wallings, R. L., & Tansey, M. G. (2025) · Communications Biology · doi:10.1038/s42003-025-08088-7 · Cited by 14
Potential of chimeric antigen receptor ( CAR )‐redirected immune cells in breast cancer therapies: Recent advances
Nikoo, M., Rudiansyah, M., Bokov, D. O., Jainakbaev, N. T., Suksatan, W., Ansari, M. J., Thangavelu, L. P., Chupradit, S., Zamani, A., Adili, A., et al. (2022) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.17465 · Cited by 12
Mechanisms of Resistance to CAR T-Cells and How to Overcome Them
Legato, L., Bisio, M., Fasano, F., Savelli, C. B., Secreto, C., Dellacasa, C. M., Botto, B., Busca, A., Cerrano, M., Freilone, R., et al. (2025) · Methods and Protocols · doi:10.3390/mps8050108 · Cited by 14
T cell aging and exhaustion: Mechanisms and clinical implications
Zhang, W., Kong, D., Zhang, X., Hu, L., Nian, Y., & Shen, Z. (2025) · Clinical Immunology · doi:10.1016/j.clim.2025.110486 · Cited by 13
Targeting CD276 with Adapter-CAR T-cells provides a novel therapeutic strategy in small cell lung cancer and prevents CD276-dependent fratricide
Kristmann, B., Werchau, N., Suresh, L., Pezzuto, E. L., Scheuermann, S., Krost, S., Schilbach, K., Moustafa-Oglou, M., Mast, A., Droste, M., et al. (2025) · Journal of Hematology & Oncology · doi:10.1186/s13045-025-01729-8 · Cited by 12
Defining and targeting patterns of T cell dysfunction in inborn errors of immunity
Campos, J. S., & Henrickson, S. E. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.932715 · Cited by 12
A Biological Perspective of TLR8 Signaling in Host Defense and Inflammation
Bian, F., Yan, D., Wu, X., & Yang, C. (2023) · Infectious Microbes & Diseases · doi:10.1097/im9.0000000000000119 · Cited by 11
MAIT cells and their implication in human oral diseases
Jiang, Q. L., Wang, F., Yang, J., & Zhou, G. (2022) · Inflammation Research · doi:10.1007/s00011-022-01600-3 · Cited by 14
Immune-based cancer therapies: mechanistic insights, clinical progress, and future directions
Devaraji, M., & Cheriyan, B. V. (2025) · Journal of the Egyptian National Cancer Institute · doi:10.1186/s43046-025-00319-6 · Cited by 16
Immunosenescence: Molecular Mechanisms, Diseases, and Therapeutic Innovations
Gong, N., Pan, X., Deng, Y., Che, J., Bao, J., Wang, M., Xu, C., Liu, X., & Shi, Y. (2025) · MedComm · doi:10.1002/mco2.70515 · Cited by 14
Chemotherapy-induced acceleration of DNA methylation-based biological age in breast cancer
Nannini, D. R., Cortese, R., VonTungeln, C. D., & Hildebrandt, G. C. (2024) · Epigenetics · doi:10.1080/15592294.2024.2360160 · Cited by 10
Tumor immune microenvironment remodeling after neoadjuvant therapy in gastric cancer: Update and new challenges
Sun, F., Gao, X., Li, T., Zhao, X., & Zhu, Y. (2025) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2025.189350 · Cited by 13
Advancing T-cell immunotherapy for cellular senescence and disease: Mechanisms, challenges, and clinical prospects
Wu, J., Zhang, L., Zhao, Z., Liu, Y., Li, Z., Feng, X., Zhang, L., Yao, X., Du, J., Chen, L., et al. (2025) · Ageing Research Reviews · doi:10.1016/j.arr.2025.102783 · Cited by 10
Differential susceptibility and role for senescence in CART cells based on costimulatory domains
Can, İ., Siegler, E. L., Sirpilla, O. L., Manriquez-Roman, C., Yun, K., Stewart, C. M., Feigin, J. M., Rodriguez, M. L., Gutierrez-Ruiz, O. L., Ogbodo, E. J., et al. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02371-1 · Cited by 11
Immune Checkpoint Molecules in Hodgkin Lymphoma and Other Hematological Malignancies
Alibrahim, M. N., Carbone, A., Alsaleh, N., & Gloghini, A. (2025) · Cancers · doi:10.3390/cancers17142292 · Cited by 13
Identification of several senescence‐associated genes signature in head and neck squamous cell carcinoma
Wang, J., Zhou, C., Sun, H., Li, Q., Hu, J., Jiang, T., & Zhou, S. (2022) · Journal of Clinical Laboratory Analysis · doi:10.1002/jcla.24555 · Cited by 10
International expert group collaboration for developing an adverse outcome pathway for radiation induced leukemia
Klokov, D. Y., Applegate, K. E., Badie, C., Brede, D. A., Dekkers, F., Karabulutoglu, M., Le, Y., Rutten, E. A., Lumniczky, K., & Gomolka, M. (2022) · International Journal of Radiation Biology · doi:10.1080/09553002.2022.2117873 · Cited by 11
Autophagic flux restoration of senescent T cells improves antitumor activity of TCR ‐engineered T cells
Zhang, C., Sun, Y., Li, S., Shen, L., Teng, X., Xiao, Y., Zhou, P., & Lu, Z. (2022) · Clinical & Translational Immunology · doi:10.1002/cti2.1419 · Cited by 10
Multi-omics analysis reveals a molecular landscape of the early recurrence and early metastasis in pan-cancer
He, D., Wang, N., Wen, X.-L., Li, X., Guo, Y. L., Fu, S.-H., Xiong, F.-F., Wu, Z.-Y., Xu, Z., Gao, X., et al. (2023) · Frontiers in Genetics · doi:10.3389/fgene.2023.1061364 · Cited by 10
High Levels of CD244 Rather Than CD160 Associate With CD8+ T-Cell Aging
Wang, X., Wang, D., Du, J., Wei, Y., Song, R., Wang, B., Qiu, S., Li, B., Zhang, L., Zeng, Y., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.853522 · Cited by 10
T Cell Defects and Immunotherapy in Chronic Lymphocytic Leukemia
Vlachonikola, E., Σταματόπουλος, Κ., & Chatzidimitriou, A. (2021) · Cancers · doi:10.3390/cancers13133255 · Cited by 10
Cytomegalovirus retinitis in patients of non-Hodgkin’s lymphoma: clinical presentations and outcomes
Reddy, S., Tyagi, M., Behera, S., Pappuru, R. R., Dave, V. P., Basu, S., & Agrawal, H. (2021) · Journal of Ophthalmic Inflammation and Infection · doi:10.1186/s12348-021-00257-z · Cited by 9
CTLA-4 blockade in ovarian cancer immunotherapy: Mechanisms and clinical strategies
Hsu, C., Muhammed, T. M., Uthirapathy, S., Ahmad, I., Ballal, S., Kalia, R., Premkumar, J., Ray, S., Mohsin, R. M., & Abiess, A. A. A. (2025) · Seminars in Oncology · doi:10.1016/j.seminoncol.2025.152370 · Cited by 11
Immunosenescence and organoids: pathophysiology and therapeutic opportunities
Kamroo, A., Kakroudi, M. H., Sarmadian, A. J., Firouzabadi, A., Mousavi, S., Yazdanpanah, N., Saleki, K., & Rezaei, N. (2025) · Immunity & Ageing · doi:10.1186/s12979-025-00530-y · Cited by 12
“Dissecting the role of T cell exhaustion in cancer progression: a multifaceted approach“
Li, X., & Song, S. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1646292 · Cited by 12
Above and beyond senescence and CAR T cell: advances and future perspectives
Rosas-Campos, R., Arceo-Orozco, S., Sandoval-Rodriguez, A. S., Madrigal, J. A., & Armendáriz‐Borunda, J. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1701655 · Cited by 10
Peripheral differentiation patterns of human T cells
Heikkilä, N., Hetemäki, I., Sormunen, S., Isoniemi, H., Kekäläinen, E., Saramäki, J., & Arstila, T. P. (2022) · European Journal of Immunology · doi:10.1002/eji.202149465 · Cited by 10
A β-glucan from Aureobasidium pullulans enhanced the antitumor effect with rituximab against SU-DHL-8
Liao, Y., Wang, R., Qin, X., Ma, X., Liu, X., Jia, S., & Zhong, C. F. (2022) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2022.09.106 · Cited by 10
The effect of neoadjuvant chemotherapy on the tumor immune microenvironment in gastrointestinal tumors
Wang, Y., Gao, P., Hao, Z., Ling, C., Li, X., Yuan, J., Liu, J., Li, J., Zhang, Y., Peng, X., et al. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.1054598 · Cited by 10
Senescent T Cells as a Resistance Mechanism to Lung Cancer Immunotherapy
Salas‐Benito, D., Eguren‐Santamaría, I., & Sanmamed, M. F. (2020) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-3507 · Cited by 9
Treatment of Multiple Primary Malignancies With PD-1 Inhibitor Camrelizumab: A Case Report and Brief Literature Review
Wan, Y., Wang, Z., Yang, N., & Liu, F. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.911961 · Cited by 9
Oncogenic signaling pathway dysregulation landscape reveals the role of pathways at multiple omics levels in pan-cancer
Wang, N., He, D., Wu, Z.-Y., Xu, Z., Wen, X.-L., Li, X., Guo, Y. A., Wang, H., & Wang, Z. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.916400 · Cited by 8
Executable models of immune signaling pathways in HIV-associated atherosclerosis
Palshikar, M. G., Palli, R., Tyrell, A., Maggirwar, S. B., Schifitto, G., Singh, M. V., & Thakar, J. (2022) · npj Systems Biology and Applications · doi:10.1038/s41540-022-00246-5 · Cited by 10
Changes in T lymphocyte subsets in peripheral blood of patients with middle-advanced cervical cancer before and after nimotuzumab combined with concurrent chemoradiotherapy
Ao, M., Li, P., Sun, D., Li, X., Xu, S., & Hao, Y. (2023) · Journal of Obstetrics and Gynaecology · doi:10.1080/01443615.2023.2179915 · Cited by 9
T-cell senescence: Unlocking the tumor immune “Dark Box” - A multidimensional analysis from mechanism to tumor immunotherapeutic intervention
Cheng, J., Zheng, J., Ma, C., Li, Y., & Hao, H. (2025) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2025.05.010 · Cited by 8
Tofacitinib treatment of rheumatoid arthritis increases senescent T cell frequency in patients and limits T cell function in vitro
Alamino, V. A., Onofrio, L. I., Acosta, C. D. V., Ferrero, P. V., Zacca, E. R., Cadile, I. I., Mussano, E. D., Onetti, L. B., Montes, C. L., Gruppi, A., et al. (2023) · European Journal of Immunology · doi:10.1002/eji.202250353 · Cited by 10
Portraying the dark side of endogenous IFN-λ for promoting cancer progression and immunoevasion in pan-cancer
Wang, Z. Z., Wen, X. L., Wang, N., Li, X. H., Yu, G., Xu, Z., Fu, S., Xiong, F. F., Li, J., Wang, L., et al. (2023) · Journal of Translational Medicine · doi:10.1186/s12967-023-04453-4 · Cited by 8
PD-1+ T lymphocyte proportions and hospitalized exacerbation of COPD: a prospective cohort study
Xue, H., Lan, X., Xue, T., Tang, X., Yang, H., Hu, Z., Xu, N., & Xie, B. (2024) · Respiratory Research · doi:10.1186/s12931-024-02847-6 · Cited by 8
Aging and immunity: the age-old tangoPreprint
Fernández-Maestre, I., Harris, A. S., & Amor, C. (2025) · Genes & Development · doi:10.1101/gad.352644.125 · Cited by 8

Authors: Zhao, Y., Shao, Q., & Peng, G.
Affiliations: Jiangsu University (CN)
Saint Louis University (US)
Corresponding author: Peng, Guangyong
ORCID: Zhao, Yangjing
Shao, Qixiang
Peng, Guangyong
Venue: Cellular & Molecular Immunology
Publisher: Springer Science and Business Media LLC
Published: 2019-12-18
Volume: 17
Issue: 1
Pages: 27-35
ISSN: 1672-7681 (ISSN-L)
2042-0226
DOI: 10.1038/s41423-019-0344-8
PMC: PMC6952436
OpenAlex: W2995437528
Cited by: 382
References: 140
Citations by year: 2026: 39 · 2025: 90 · 2024: 70 · 2023: 59 · 2022: 61 · 2021: 45 · 2020: 18
FWCI: 2.95
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Cellular and Molecular Immunology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: American Cancer Society (RSG-10-160-01-LIB)
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 exhaustion, T cell senescence, tumor-infiltrating T cells, tumor microenvironment, antitumor immunity, immunotherapy resistance, T cell metabolism, metabolic signaling pathways, cancer immunotherapy
MeSH terms: Animals, Humans, Immunotherapy, Neoplasms, T-Lymphocytes, Lymphocytes, Tumor-Infiltrating, Cellular Senescence, Tumor Microenvironment

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 ›

Are you an author, or do you see a problem with this page? Request a review

Exhaustion and senescence: two crucial dysfunctional states of T cells in the tumor microenvironment

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks