
CARD11 signaling regulates CD8+ T cell tumoricidal function
Hashimoto, M. et al. CD8 T cell exhaustion in chronic infection and cancer: opportunities for interventions. Annu. Rev. Med. 69, 301–318 (2018).
Giles, J. R., Globig, A.-M., Kaech, S. M. & Wherry, E. J. CD8+ T cells in the cancer-immunity cycle. Immunity 56, 2231–2253 (2023).
McLane, L. M., Abdel-Hakeem, M. S. & Wherry, E. J. CD8 T cell exhaustion during chronic viral infection and cancer. Annu. Rev. Immunol. 37, 457–495 (2019).
Li, H. et al. Dysfunctional CD8 T cells form a proliferative, dynamically regulated compartment within human melanoma. Cell 176, 775–789.e18 (2019).
Philip, M. & Schietinger, A. CD8+ T cell differentiation and dysfunction in cancer. Nat. Rev. Immunol. 22, 209–223 (2022).
ElTanbouly, M. A. & Noelle, R. J. Rethinking peripheral T cell tolerance: checkpoints across a T cell’s journey. Nat. Rev. Immunol. 21, 257–267 (2021).
Liu, Y. & Zheng, P. Preserving the CTLA-4 checkpoint for safer and more effective cancer immunotherapy. Trends Pharmacol. Sci. 41, 4–12 (2020).
Wu, J. E. et al. In vitro modeling of CD8+ T cell exhaustion enables CRISPR screening to reveal a role for BHLHE40. Sci. Immunol. 8, eade3369 (2023).
Thome, M., Charton, J. E., Pelzer, C. & Hailfinger, S. Antigen receptor signaling to NF-κB via CARMA1, BCL10, and MALT1. Cold Spring Harb. Perspect. Biol. 2, a003004 (2010).
Jun, J. E. & Goodnow, C. C. Scaffolding of antigen receptors for immunogenic versus tolerogenic signaling. Nat. Immunol. 4, 1057–1064 (2003).
Snow, A. L. et al. Congenital B cell lymphocytosis explained by novel germline CARD11 mutations. J. Exp. Med. 209, 2247–2261 (2012).
Lenz, G. et al. Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science 319, 1676–1679 (2008).
Wei, Z. et al. Pathogenic CARD11 mutations affect B cell development and differentiation through a noncanonical pathway. Sci. Immunol. 4, eaaw5618 (2019).
Leong, Y. A. et al. CXCR5(+) follicular cytotoxic T cells control viral infection in B cell follicles. Nat. Immunol. 17, 1187–1196 (2016).
He, R. et al. Follicular CXCR5-expressing CD8(+) T cells curtail chronic viral infection. Nature 537, 412–428 (2016).
Wu, T. et al. The TCF1–Bcl6 axis counteracts type I interferon to repress exhaustion and maintain T cell stemness. Sci. Immunol. 1, eaai8593 (2016).
Utzschneider, D. T. et al. T cell factor 1-expressing memory-like CD8(+) T cells sustain the immune response to chronic viral infections. Immunity 45, 415–427 (2016).
Im, S. J. et al. Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy. Nature 537, 417–421 (2016).
Thommen, D. S. et al. A transcriptionally and functionally distinct PD-1+CD8+ T cell pool with predictive potential in non-small-cell lung cancer treated with PD-1 blockade. Nat. Med. 24, 994–1004 (2018).
Scott, A. C. et al. TOX is a critical regulator of tumour-specific T cell differentiation. Nature 571, 270–274 (2019).
Khan, O. et al. TOX transcriptionally and epigenetically programs CD8+ T cell exhaustion. Nature 571, 211–218 (2019).
Alfei, F. et al. TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection. Nature 571, 265–269 (2019).
Beltra, J.-C. et al. Developmental relationships of four exhausted CD8+ T cell subsets reveals underlying transcriptional and epigenetic landscape control mechanisms. Immunity 52, 825–841.e8 (2020).
Duhen, T. et al. Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors. Nat. Commun. 9, 2724 (2018).
Oliveira, G. et al. Phenotype, specificity and avidity of antitumour CD8+ T cells in melanoma. Nature 596, 119–125 (2021).
Liu, B. et al. Temporal single-cell tracing reveals clonal revival and expansion of precursor exhausted T cells during anti-PD-1 therapy in lung cancer. Nat. Cancer 3, 108–121 (2022).
Zhang, L. et al. Lineage tracking reveals dynamic relationships of T cells in colorectal cancer. Nature 564, 268–272 (2018).
Gaide, O. et al. CARMA1 is a critical lipid raft-associated regulator of TCR-induced NF-κB activation. Nat. Immunol. 3, 836–843 (2002).
Lamason, R. L., Kupfer, A. & Pomerantz, J. L. The dynamic distribution of CARD11 at the immunological synapse is regulated by the inhibitory kinesin GAKIN. Mol. Cell 40, 798–809 (2010).
Luton, F., Legendre, V., Gorvel, J. P., Schmitt-Verhulst, A. M. & Boyer, C. Tyrosine and serine protein kinase activities associated with ligand-induced internalized TCR/CD3 complexes. J. Immunol. 158, 3140–3147 (1997).
Evnouchidou, I. et al. IRAP-dependent endosomal T cell receptor signalling is essential for T cell responses. Nat. Commun. 11, 2779 (2020).
Phelan, J. D. et al. A multiprotein supercomplex controlling oncogenic signalling in lymphoma. Nature 560, 387–391 (2018).
Evnouchidou, I., Caillens, V., Koumantou, D. & Saveanu, L. The role of endocytic trafficking in antigen T cell receptor activation. Biomed. J. 45, 310–320 (2022).
Ouchida, R. et al. A lysosomal protein negatively regulates surface T cell antigen receptor expression by promoting CD3ζ-chain degradation. Immunity 29, 33–43 (2008).
Chiffelle, J. et al. T-cell repertoire analysis and metrics of diversity and clonality. Curr. Opin. Biotechnol. 65, 284–295 (2020).
Altman, J. D. et al. Phenotypic analysis of antigen-specific T lymphocytes. Science 274, 94–96 (1996).
Simoni, Y. et al. Bystander CD8+ T cells are abundant and phenotypically distinct in human tumour infiltrates. Nature 557, 575–579 (2018).
Kataoka, T. et al. Concanamycin A, a powerful tool for characterization and estimation of contribution of perforin- and Fas-based lytic pathways in cell-mediated cytotoxicity. J. Immunol. 156, 3678–3686 (1996).
Miller, B. C. et al. Subsets of exhausted CD8+ T cells differentially mediate tumor control and respond to checkpoint blockade. Nat. Immunol. 20, 326–336 (2019).
Westcott, P. M. K. et al. Mismatch repair deficiency is not sufficient to elicit tumor immunogenicity. Nat. Genet. (2023).
Yost, K. E. et al. Clonal replacement of tumor-specific T cells following PD-1 blockade. Nat. Med. 25, 1251–1259 (2019).
Han, J. et al. TCR repertoire diversity of peripheral PD-1+CD8+ T cells predicts clinical outcomes after immunotherapy in patients with non-small cell lung cancer. Cancer Immunol. Res. 8, 146–154 (2020).
Piehl, N. et al. Cerebrospinal fluid immune dysregulation during healthy brain aging and cognitive impairment. Cell 185, 5028–5039.e13 (2022).
Shakiba, M. et al. TCR signal strength defines distinct mechanisms of T cell dysfunction and cancer evasion. J. Exp. Med. 219, e20201966 (2022).
Singhaviranon, S., Dempsey, J. P., Hagymasi, A. T., Mandoiu, I. I. & Srivastava, P. K. Low-avidity T cells drive endogenous tumor immunity in mice and humans. Nat. Immunol. 26, 240–251 (2025).
Saeidi, A. et al. T-cell exhaustion in chronic infections: reversing the state of exhaustion and reinvigorating optimal protective immune responses. Front. Immunol. 9, 2569 (2018).
Jhunjhunwala, S., Hammer, C. & Delamarre, L. Antigen presentation in cancer: insights into tumour immunogenicity and immune evasion. Nat. Rev. Cancer 21, 298–312 (2021).
Yang, K., Halima, A. & Chan, T. A. Antigen presentation in cancer — mechanisms and clinical implications for immunotherapy. Nat. Rev. Clin. Oncol. 20, 604–623 (2023).
Garcia, J. et al. Naturally occurring T cell mutations enhance engineered T cell therapies. Nature 626, 626–634 (2024).