Exhaustion of tumor-specific CD8+ T cells in metastases from melanoma patients
Open accessAbstract
In chronic viral infections, CD8⁺ T cells become functionally deficient and display multiple molecular alterations. In contrast, only little is known of self- and tumor-specific CD8⁺ T cells from mice and humans. Here we determined molecular profiles of tumor-specific CD8⁺ T cells from melanoma patients. In peripheral blood from patients vaccinated with CpG and the melanoma antigen Melan-A/MART-1 peptide, we found functional effector T cell populations, with only small but nevertheless significant differences in T cells specific for persistent herpesviruses (EBV and CMV). In contrast, Melan-A/MART-1-specific T cells isolated from metastases from patients with melanoma expressed a large variety of genes associated with T cell exhaustion. The identified exhaustion profile revealed extended molecular alterations. Our data demonstrate a remarkable coexistence of effector cells in circulation and exhausted cells in the tumor environment. Functional T cell impairment is mediated by inhibitory receptors and further molecular pathways, which represent potential targets for cancer therapy.
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
Cites
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?
Exhausted T cells can occur in cancer, not only in chronic viral infections.
“Originally described in the context of chronic viral infections, where the host fails to clear the pathogen, it is now apparent that exhausted T cells can also occur in cancer (12, 13).”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [13]
PD-1 has been detected on circulating tumor-specific T cells and tumor-infiltrating lymphocytes, where it was associated with decreased T cell function in humans and mice.
“The inhibitory receptor has been detected on both circulating tumor-specific T cells and tumor-infiltrating lymphocytes, where it was associated with decreased T cell function in humans and mice (13, 29, 55–57).”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [13]
PD-L1 on tumor cells or other infiltrating immune cells can disable PD-1-expressing tumor-infiltrating T cells.
“PD-1-expressing tumor-infiltrating T cells can be disabled by PD-L1 on the surfaces of tumor cells or other infiltrating immune cells, and blocking antibodies targeting PD-1 signaling are therefore thought to mainly affect the effector stage of the immune response (13, 55–57).”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [13]
Blocking antibodies targeting PD-1 signaling mainly affect the effector stage of the immune response.
“PD-1-expressing tumor-infiltrating T cells can be disabled by PD-L1 on the surfaces of tumor cells or other infiltrating immune cells, and blocking antibodies targeting PD-1 signaling are therefore thought to mainly affect the effector stage of the immune response (13, 55–57).”
From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [13]
LAG3 highly expressed on tumor-infiltrating lymphocytes interacts with tumor cell surface ligands to cause T cell dysfunction or exhaustion, promoting tumor immune escape, particularly in CD8+ T cells.
“LAG3, highly expressed on the tumor‐infiltrating lymphocytes (TILs), interacts with ligands located on the surface of tumor cells to cause T cell dysfunction or even exhaustion, promoting tumor immune escape, particularly evident in CD8+ T cells [329, 330].”
From Tumor microenvironment signaling and therapeutics in cancer progression (2023) · cites this paper as [329]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625 · see citing works
Molecular Signature of CD8+ T Cell Exhaustion during Chronic Viral Infection
Wherry, E. J., Ha, S.-J., Kaech, S. M., Haining, W. N., Sarkar, S., Kalia, V., Subramaniam, S., Blattman, J. N., Barber, D. L., & Ahmed, R. (2007) · Immunity · doi:10.1016/j.immuni.2007.09.006 · Cited by 2,103 · see citing works
Ahmadzadeh, M., Johnson, L. A., Heemskerk, B., Wunderlich, J. R., Dudley, M. E., White, D. E., & Rosenberg, S. A. (2009) · Blood · doi:10.1182/blood-2008-12-195792 · Cited by 1,766 · see citing works
Bengsch, B., Seigel, B., Ruhl, M., Timm, J., Kuntz, M., Blum, H. E., Pircher, H., & Thimme, R. (2010) · PLoS Pathogens · doi:10.1371/journal.ppat.1000947 · Cited by 373 · see citing works
Hadrup, S. R., Bakker, A. H., Shu, C. J., Andersen, R. S., van Veluw, J., Hombrink, P., Castermans, E., thor Straten, P., Blank, C., Haanen, J. B., et al. (2009) · Nature Methods · doi:10.1038/nmeth.1345 · Cited by 306 · see citing works
Flagged first, then by citations
Research works printed but not linked: 44
- Kim PS, Ahmed R. Features of responding T cells in cancer and chronic infection. Curr Opin Immunol. 2010;22(2):223-230.
- Turner SJ, Kedzierska K, La Gruta NL, Webby R, Doherty PC. Characterization of CD8+ T cell rep- ertoire diversity and persistence in the influenza A virus model of localized, transient infection. Semin Immunol. 2004;16(3):179-184.
- Gallimore A, Hengartner H, Zinkernagel R. Hierar- chies of antigen-specific cytotoxic T cell responses. Immunol Rev. 1998;164:29-36.
- Yewdell JW, Bennink JR. Immunodominance in major histocompatibility complex class I-restricted T lymphocyte responses. Annu Rev Immunol. 1999; 17:51-88.
- Appay V, Douek DC, Price DA. CD8+ T cell effi- cacy in vaccination and disease. Nat Med. 2008; 14(6):623-628.
- Appay V, Rowland-Jones SL. Lessons from the study of T cell differentiation in persistent human virus infection. Semin Immunol. 2004;16(3):205-212.
- Makedonas G, et al. Perforin and IL-2 upregulation define qualitative differences among highly func- tional virus-specific human CD8 + T cells. PLoS Pathog. 2010;6(3):e1000798.
- Chen SF, et al. Antiviral CD8 + T cells in the control of primary human cytomegalovirus infection in early childhood. J Infect Dis. 2004;189(9):1619-1627.
- Guerreiro M, et al. Human peripheral blood and bone marrow Epstein-Barr virus-specific T cell rep- ertoire in latent infection reveals distinct memory T cell subsets. Eur J Immunol. 2010;40(6):1566-1576.
- Zajac AJ, et al. Viral immune evasion due to persis- tence of activated T cells without effector function. J Exp Med. 1998;188(12):2205-2213.
- Moskophidis D, Lechner F, Pircher H, Zinkernagel RM. Virus persistence in acutely infected immuno- competent mice by exhaustion of antiviral cytotoxic effector T cells. Nature. 1993;362(6422):758-761.
- Wherry EJ, Blattman JN, Murali-Krishna K, van der Most R, Ahmed R. Viral persistence alters CD8 + T cell immunodominance and tissue distribution and results in distinct stages of functional impairment. J Virol. 2003;77(8):4911-4927.
- Yi JS, Cox MA, Zajac AJ. T cell exhaustion: charac- teristics, causes and conversion. Immunology. 2010; 129(4):474-481.
- Barber DL, et al. Restoring function in exhausted CD8 + T cells during chronic viral infection. Nature. 2006;439(7077):682-687.
- Rehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol. 2005;5(3):215-229.
- Letvin NL, Walker BD. Immunopathogenesis and immunotherapy in AIDS virus infections. Nat Med. 2003;9(7):861-866.
- Quigley M, et al. Transcriptional analysis of HIV- specific CD8(+) T cells shows that PD-1 inhibits T cell function by upregulating BATF. Nat Med. 2010; 16(10):1147-1151.
- Speiser DE, et al. Rapid and strong human CD8+ T cell responses to vaccination with peptide, IFA, and CpG oligodeoxynucleotide 7909. J Clin Invest. 2005;115(3):739-746.
- Zippelius A, et al. Effector function of human tumor-specific CD8 + T cells in melanoma lesions: a state of local functional tolerance. Cancer Res. 2004; 64(8):2865-2873.
- Speiser DE, et al. Memory and effector CD8 + T cell responses after nanoparticle vaccination of mela- noma patients. J Immunother. 2010;33(8):848-858.
- Rosenberg SA, Dudley ME. Adoptive cell therapy for the treatment of patients with metastatic melanoma. Curr Opin Immunol. 2009;21(2):233-240.
- Sakuishi K, Apetoh L, Sullivan JM, Blazar BR, Kuchroo VK, Anderson AC. Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. J Exp Med. 2010; 207(10):2187-2194.
- Appay V, et al. New generation vaccine induces effective melanoma-specific CD8+ T cells in the cir- culation but not in the tumor site. J Immunol. 2006; 177(3):1670-1678.
- Choi S, Schwartz RH. Molecular mechanisms for adaptive tolerance and other T cell anergy models. Semin Immunol. 2007;19(3):140-152.
- Derre L, et al. BTLA mediates inhibition of human tumor-specific CD8+ T cells that can be par- tially reversed by vaccination. J Clin Invest. 2010; 120(1):157-167.
- Appay V, et al. Sensitive gene expression profiling of human T cell subsets reveals parallel post-thy- mic differentiation for CD4+ and CD8+ lineages. J Immunol. 2007;179(11):7406-7414.
- Critchley-Thorne RJ, Yan N, Nacu S, Weber J, Holmes SP, Lee PP. Down-regulation of the interferon signal- ing pathway in T lymphocytes from patients with metastatic melanoma. PLoS Med. 2007;4(5):e176.
- Cham CM, Xu H, O'Keefe JP, Rivas FV, Zagouras P, Gajewski TF. Gene array and protein expression pro- files suggest post-transcriptional regulation dur- ing CD8+ T cell differentiation. J Biol Chem. 2003; 278(19):17044-17052.
- Willinger T, Freeman T, Hasegawa H, McMichael AJ, Callan MF. Molecular signatures distinguish human central memory from effector memory CD8 + T cell subsets. J Immunol. 2005;175(9):5895-5903.
- Blackburn SD, et al. Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors dur- ing chronic viral infection. Nat Immunol. 2009; 10(1):29-37.
- Jin HT, et al. Cooperation of Tim-3 and PD-1 in CD8 + T cell exhaustion during chronic viral infection. Proc Natl Acad Sci U S A. 2010;107(33):14733-14738.
- Rey J, et al. The co-expression of 2B4 (CD244) and CD160 delineates a subpopulation of human CD8+ T cells with a potent CD160-mediated cytolytic effec- tor function. Eur J Immunol. 2006;36(9):2359-2366.
- Fourcade J, et al. Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen-specif- ic CD8+ T cell dysfunction in melanoma patients. J Exp Med. 2010;207(10):2175-2186.
- McMahan RH, et al. Tim-3 expression on PD-1+ HCV-specific human CTLs is associated with viral persistence, and its blockade restores hepa- tocyte-directed in vitro cytotoxicity. J Clin Invest. 2010;120(12):4546-4557.
- Macian F, Garcia-Cozar F, Im SH, Horton HF, Byrne MC, Rao A. Transcriptional mechanisms underlying lymphocyte tolerance. Cell. 2002;109(6):719-731.
- Parish IA, et al. The molecular signature of CD8+ T cells undergoing deletional tolerance. Blood. 2009;113(19):4575-4585.
- Willimsky G, Blankenstein T. Sporadic immuno- genic tumours avoid destruction by inducing T cell tolerance. Nature. 2005;437(7055):141-146.
- Willimsky G, et al. Immunogenicity of premalig- nant lesions is the primary cause of general cytotox- ic T lymphocyte unresponsiveness. J Exp Med. 2008; 205(7):1687-1700.
- Miller JD, et al. Human effector and memory CD8+ T cell responses to smallpox and yellow fever vaccines. Immunity. 2008;28(5):710-722.
- Gaucher D, et al. Yellow fever vaccine induces inte- grated multilineage and polyfunctional immune responses. J Exp Med. 2008;205(13):3119-3131.
- Barbey C, et al. IL-12 controls cytotoxicity of a novel subset of self-antigen-specific human CD28+ cyto- lytic T cells. J Immunol. 2007;178(6):3566-3574.
- Lienard D, et al. Ex vivo detectable activation of Melan-A-specific T cells correlating with inflam- matory skin reactions in melanoma patients vaccinated with peptides in IFA. Cancer Immun. 2004;4:4.
- Romero P, et al. Ex vivo staining of metastatic lymph nodes by class I major histocompatibility complex tetramers reveals high numbers of anti- gen-experienced tumor-specific cytolytic T lym- phocytes. J Exp Med. 1998;188(9):1641-1650.
- Roederer M, Nozzi JL, Nason MC. SPICE: Explora- tion and analysis of post-cytometric complex multi- variate datasets. Cytometry A. 2011;79(2):167-174.
Cited by
Sorted by citations
Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq
Tirosh, I., Izar, B., Prakadan, S. M., Wadsworth, M. H., Treacy, D., Trombetta, J. J., Rotem, A., Rodman, C., Lian, C., Murphy, G., et al. (2016) · Science · doi:10.1126/science.aad0501 · Cited by 4,944 · see citing works
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 · see citing works
The Tumour Microenvironment after Radiotherapy: Mechanisms of Resistance and Recurrence
Barker, H. E., Paget, J. T. E., Khan, A. A., & Harrington, K. J. (2015) · Nature Reviews Cancer · doi:10.1038/nrc3958 · Cited by 2,144 · see citing works
Miller, B. C., Sen, D. R., Al Abosy, R., Bi, K., Virkud, Y. V., LaFleur, M. W., Yates, K. B., Lako, A., Felt, K., Naik, G. S., et al. (2019) · Nature Immunology · doi:10.1038/s41590-019-0312-6 · Cited by 2,087 · see citing works
Siddiqui, I., Schaeuble, K., Chennupati, V., Fuertes Marraco, S. A., Calderon-Copete, S., Pais Ferreira, D., Carmona, S. J., Scarpellino, L., Gfeller, D., Pradervand, S., et al. (2019) · Immunity · doi:10.1016/j.immuni.2018.12.021 · Cited by 1,679 · see citing works
Self-citationT cell costimulatory receptor CD28 is a primary target for PD-1–mediated inhibition
Hui, E., Cheung, J., Zhu, J., Su, X., Taylor, M. J., Wallweber, H. A., Sasmal, D. K., Huang, J., Kim, J. M., Mellman, I., et al. (2017) · Science · doi:10.1126/science.aaf1292 · Cited by 1,689 · see citing works
Adoptive immunotherapy for cancer: harnessing the T cell response
Restifo, N. P., Dudley, M. E., & Rosenberg, S. A. (2012) · Nature Reviews Immunology · doi:10.1038/nri3191 · Cited by 1,688 · see citing works
Bystander CD8+ T cells are abundant and phenotypically distinct in human tumour infiltrates
Simoni, Y., Becht, E., Fehlings, M., Loh, C. Y., Koo, S.-L., Teng, K. W. W., Yeong, J. P. S., Nahar, R., Zhang, T., Kared, H., et al. (2018) · Nature · doi:10.1038/s41586-018-0130-2 · Cited by 1,370 · see citing works
Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations
Seidel, J. A., Otsuka, A., & Kabashima, K. (2018) · Frontiers in Oncology · doi:10.3389/fonc.2018.00086 · Cited by 1,360 · see citing works
Thommen, D. S., Koelzer, V. H., Herzig, P., Roller, A., Trefny, M., Dimeloe, S., Kiialainen, A., Hanhart, J., Schill, C., Hess, C., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0057-z · Cited by 1,161 · see citing works
VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors
Voron, T., Colussi, O., Marcheteau, E., Pernot, S., Nizard, M., Pointet, A.-L., Latreche, S., Bergaya, S., Benhamouda, N., Tanchot, C., et al. (2015) · Journal of Experimental Medicine · doi:10.1084/jem.20140559 · Cited by 1,179 · see citing works
TOX is a critical regulator of tumour-specific T cell differentiation
Scott, A. C., Dündar, F., Zumbo, P., Chandran, S. S., Klebanoff, C. A., Shakiba, M., Trivedi, P., Menocal, L., Appleby, H., Camara, S., et al. (2019) · Nature · doi:10.1038/s41586-019-1324-y · Cited by 1,106 · see citing works
Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors
Duhen, T., Duhen, R., Montler, R., Moses, J., Moudgil, T., de Miranda, N. F., Goodall, C. P., Blair, T. C., Fox, B. A., McDermott, J. E., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05072-0 · Cited by 938 · see citing works
Schietinger, A., Philip, M., Krisnawan, V. E., Chiu, E. Y., Delrow, J. J., Basom, R. S., Lauer, P., Brockstedt, D. G., Knoblaugh, S. E., Hämmerling, G. J., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.07.011 · Cited by 720 · see citing works
T cell anergy, exhaustion, senescence, and stemness in the tumor microenvironment
Crespo, J., Sun, H., Welling, T. H., Tian, Z., & Zou, W. (2013) · Current Opinion in Immunology · doi:10.1016/j.coi.2012.12.003 · Cited by 752 · see citing works
T-cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection
McKinney, E. F., Lee, J. C., Jayne, D. R. W., Lyons, P. A., & Smith, K. G. C. (2015) · Nature · doi:10.1038/nature14468 · Cited by 685 · see citing works
Checkpoint Blockade Immunotherapy Induces Dynamic Changes in PD-1-CD8+ Tumor-Infiltrating T Cells
Kurtulus, S., Madi, A., Escobar, G., Klapholz, M., Nyman, J., Christian, E., Pawlak, M., Dionne, D., Xia, J., Rozenblatt-Rosen, O., et al. (2019) · Immunity · doi:10.1016/j.immuni.2018.11.014 · Cited by 636 · see citing works
Hypoxia-inducible factors enhance the effector responses of CD8(+) T cells to persistent antigen
Doedens, A. L., Phan, A. T., Stradner, M. H., Fujimoto, J. K., Nguyen, J. V., Yang, E., Johnson, R. S., & Goldrath, A. W. (2013) · Nature Immunology · doi:10.1038/ni.2714 · Cited by 660 · see citing works
Disturbed mitochondrial dynamics in CD8+ TILs reinforce T cell exhaustion
Yu, Y.-R., Imrichova, H., Wang, H., Chao, T., Xiao, Z., Gao, M., Rincon-Restrepo, M., Franco, F., Genolet, R., Cheng, W.-C., et al. (2020) · Nature Immunology · doi:10.1038/s41590-020-0793-3 · Cited by 593 · see citing works
Lakins, M. A., Ghorani, E., Munir, H., Martins, C. P., & Shields, J. D. (2018) · Nature Communications · doi:10.1038/s41467-018-03347-0 · Cited by 578 · see citing works
Meyer, C., Cagnon, L., Costa-Nunes, C. M., Baumgaertner, P., Montandon, N., Leyvraz, L., Michielin, O., Romano, E., & Speiser, D. E. (2014) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-013-1508-5 · Cited by 560 · see citing works
Self-citationLymphatic and interstitial flow in the tumour microenvironment: linking mechanobiology with immunity
Swartz, M. A., & Lund, A. W. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3186 · Cited by 544 · see citing works
Ganesan, A.-P., Clarke, J., Wood, O., Garrido-Martin, E. M., Chee, S. J., Mellows, T., Samaniego-Castruita, D., Singh, D., Seumois, G., Alzetani, A., et al. (2017) · Nature Immunology · doi:10.1038/ni.3775 · Cited by 528 · see citing works
Reversing T-cell Dysfunction and Exhaustion in Cancer
Zarour, H. M. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-1849 · Cited by 462 · see citing works
Lymphocyte-activation gene 3 (LAG3): The next immune checkpoint receptor
Ruffo, E., Wu, R. C., Bruno, T. C., Workman, C. J., & Vignali, D. A. A. (2019) · Seminars in Immunology · doi:10.1016/j.smim.2019.101305 · Cited by 381 · see citing works
TIM-3 regulates CD103+ dendritic cell function and response to chemotherapy in breast cancer
de Mingo Pulido, Á., Gardner, A., Hiebler, S., Soliman, H., Rugo, H. S., Krummel, M. F., Coussens, L. M., & Ruffell, B. (2018) · Cancer Cell · doi:10.1016/j.ccell.2017.11.019 · Cited by 388 · see citing works
Baessler, A., & Vignali, D. A. A. (2024) · Annual Review of Immunology · doi:10.1146/annurev-immunol-090222-110914 · Cited by 420 · see citing works
Exhaustion and senescence: two crucial dysfunctional states of T cells in the tumor microenvironment
Zhao, Y., Shao, Q., & Peng, G. (2020) · Cellular & Molecular Immunology · doi:10.1038/s41423-019-0344-8 · Cited by 382 · see citing works
Tumor microenvironment signaling and therapeutics in cancer progression
Goenka, A., Khan, F., Verma, B., Sinha, P., Dmello, C. C., Jogalekar, M. P., Gangadaran, P., & Ahn, B. (2023) · Cancer Communications · doi:10.1002/cac2.12416 · Cited by 323 · see citing works
Singh, N., Lee, Y. G., Shestova, O., Ravikumar, P., Hayer, K. E., Hong, S. J., Lu, X. M., Pajarillo, R., Agarwal, S., Kuramitsu, S., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0813 · Cited by 295 · see citing works
Liu, B., Zhang, Y., Wang, D., Hu, X., & Zhang, Z. (2022) · Nature Cancer · doi:10.1038/s43018-022-00433-7 · Cited by 309 · see citing works
Tumour-infiltrating lymphocytes in melanoma prognosis and cancer immunotherapy
Lee, N., Zakka, L. R., Mihm, M. C., & Schatton, T. (2016) · Pathology · doi:10.1016/j.pathol.2015.12.006 · Cited by 250 · see citing works
Collier, J. L., Weiss, S. A., Pauken, K. E., Sen, D. R., & Sharpe, A. H. (2021) · Nature Immunology · doi:10.1038/s41590-021-00949-7 · Cited by 237 · see citing works
Regulatory T cells trigger effector T cell DNA damage and senescence caused by metabolic competition
Liu, X., Mo, W., Ye, J., Li, L., Zhang, Y., Hsueh, E. C., Hoft, D. F., & Peng, G. (2018) · Nature Communications · doi:10.1038/s41467-017-02689-5 · Cited by 224 · see citing works
Sun, Z., Ren, Z., Yang, K., Liu, Z., Cao, S., Deng, S., Xu, L., Liang, Y., Guo, J., Bian, Y., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11782-w · Cited by 211 · see citing works
Huo, J.-L., Wang, Y.-T., Fu, W.-J., Lu, N., & Liu, Z.-S. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.956090 · Cited by 176 · see citing works
Trigger-happy resident memory CD4+ T cells inhabit the human lungs
Oja, A. E., Piet, B., Helbig, C., Stark, R., van der Zwan, D., Blaauwgeers, H., Remmerswaal, E. B. M., Amsen, D., Jonkers, R. E., Moerland, P. D., et al. (2018) · Mucosal Immunology · doi:10.1038/mi.2017.94 · Cited by 160 · see citing works
Seifert, A. M., Zeng, S., Zhang, J. Q., Kim, T. S., Cohen, N. A., Beckman, M. J., Medina, B. D., Maltbaek, J. H., Loo, J. K., Crawley, M. H., et al. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-1163 · Cited by 149 · see citing works
Lu, Y., Hong, B., Li, H., Zheng, Y., Zhang, M., Wang, S., Qian, J., & Yi, Q. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1317431111 · Cited by 146 · see citing works
Oja, A. E., Piet, B., van der Zwan, D., Blaauwgeers, H., Mensink, M., de Kivit, S., Borst, J., Nolte, M. A., van Lier, R. A. W., Stark, R., et al. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02654 · Cited by 130 · see citing works
Metabolic communication in tumors: a new layer of immunoregulation for immune evasion
Ho, P.-C., & Liu, P.-S. (2016) · Journal for ImmunoTherapy of Cancer · doi:10.1186/s40425-016-0109-1 · Cited by 124 · see citing works
Immune-based antitumor effects of BRAF inhibitors rely on signaling by CD40L and IFNγ
Ho, P.-C., Meeth, K. M., Tsui, Y.-C., Srivastava, B., Bosenberg, M. W., & Kaech, S. M. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-3461 · Cited by 126 · see citing works
Datta, N. R., Krishnan, S., Speiser, D. E., Neufeld, E., Kuster, N., Bodis, S., & Hofmann, H. (2016) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2016.09.016 · Cited by 92 · see citing works
Self-citationGestermann, N., Saugy, D., Martignier, C., Tillé, L., Fuertes Marraco, S. A., Zettl, M., Tirapu, I., Speiser, D. E., & Verdeil, G. (2020) · OncoImmunology · doi:10.1080/2162402x.2020.1736792 · Cited by 69 · see citing works
Self-citationT-cell exhaustion: understanding the interface of chronic viral and autoinflammatory diseases
McKinney, E. F., & Smith, K. G. (2016) · Immunology & Cell Biology · doi:10.1038/icb.2016.81 · Cited by 36 · see citing works
The biology of combination immunotherapy in recurrent metastatic head and neck cancer
Yuan, X., Yi, M., Zhang, W., Xu, L., Chu, Q., Luo, S., & Wu, K. (2021) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2021.106002 · Cited by 13 · see citing works
- Authors
- Baitsch, L., Baumgaertner, P., Devêvre, E., Raghav, S. K., Legat, A., Barba, L., Wieckowski, S., Bouzourene, H., Deplancke, B., Romero, P., Rufer, N., & Speiser, D. E.
- Affiliations
- Ludwig Cancer Research (BE)
- École Polytechnique Fédérale de Lausanne (CH)
- University of Lausanne (CH)
- Ludwig Cancer Research (CH)
- Corresponding author
- Speiser, Daniel E.
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2011-06-01
- Volume
- 121
- Issue
- 6
- Pages
- 2350-2360
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC3104769
- OpenAlex
- W1981291019
- Cited by
- 845
- References
- 5
- Citations by year
- 2026: 27 · 2025: 38 · 2024: 44 · 2023: 64 · 2022: 62 · 2021: 90 · 2020: 88 · 2019: 78 · 2018: 69 · 2017: 56 · 2016: 50 · 2015: 63 · 2014: 39 · 2013: 42 · 2012: 29
- FWCI
- 17.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- SERVAL (Université de Lausanne) (publishedVersion, other-oa)
- IRIS (submittedVersion)
- HAL (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- SERVAL (Université de Lausanne) (submittedVersion)
- Funders
- National Science Foundation
- Cancer Research Institute
- Pfizer
- Ludwig Institute for Cancer Research
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- National Center of Competence in Research Chemical Biology
- 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, CD8+ T cells, melanoma, metastasis, Melan-A/MART-1, Epstein-Barr virus, cytomegalovirus, inhibitory receptors, effector T cells, tumor microenvironment, cancer immunotherapy
- MeSH terms
- Cytomegalovirus Infections, Cytomegalovirus, Herpesvirus 4, Human, Humans, Melanoma, Molecular Sequence Data, Receptors, Immunologic, Vaccination, T-Lymphocyte Subsets, Lymphocytes, Tumor-Infiltrating, Virus Latency, CD8-Positive T-Lymphocytes, CpG Islands, Cancer Vaccines, Epstein-Barr Virus Infections, Gene Expression Profiling, T-Cell Antigen Receptor Specificity, MART-1 Antigen
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
