Reck, M., Remon, J. & Hellmann, M. D. First-line immunotherapy for non-small-cell lung cancer. J. Clin. Oncol. 40, 586–597 (2022).
Google Scholar
Lee, S. M. et al. First-line atezolizumab monotherapy versus single-agent chemotherapy in patients with non-small-cell lung cancer ineligible for treatment with a platinum-containing regimen (IPSOS): a phase 3, global, multicentre, open-label, randomised controlled study. Lancet 402, 451–463 (2023).
Google Scholar
Klocke, K., Sakaguchi, S., Holmdahl, R. & Wing, K. Induction of autoimmune disease by deletion of CTLA-4 in mice in adulthood. Proc. Natl Acad. Sci. USA 113, E2383–E2392 (2016).
Google Scholar
Sharpe, A. H. & Pauken, K. E. The diverse functions of the PD1 inhibitory pathway. Nat. Rev. Immunol. 18, 153–167 (2018).
Google Scholar
Haanen, J. et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann. Oncol. 33, 1217–1238 (2022).
Google Scholar
Luoma, A. M. et al. Molecular pathways of colon inflammation induced by cancer immunotherapy. Cell 182, 655–671 (2020).
Google Scholar
Lozano, A. X. et al. T cell characteristics associated with toxicity to immune checkpoint blockade in patients with melanoma. Nat. Med. 28, 353–362 (2022).
Google Scholar
Shankar, B. et al. Multisystem immune-related adverse events associated with immune checkpoint inhibitors for treatment of non-small cell lung cancer. JAMA Oncol. 6, 1952–1956 (2020).
Google Scholar
Won, T. et al. Cardiac myosin-specific autoimmune T cells contribute to immune-checkpoint-inhibitor-associated myocarditis. Cell Rep. 41, 111611 (2022).
Google Scholar
Wang, D. Y. et al. Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA Oncol. 4, 1721–1728 (2018).
Google Scholar
Bai, X. et al. Early use of high-dose glucocorticoid for the management of irAE is associated with poorer survival in patients with advanced melanoma treated with anti-PD-1 monotherapy. Clin. Cancer Res. 27, 5993–6000 (2021).
Google Scholar
Arbour, K. C. et al. Impact of baseline steroids on efficacy of programmed cell death-1 and programmed death-ligand 1 blockade in patients with non-small-cell lung cancer. J. Clin. Oncol. 36, 2872–2878 (2018).
Google Scholar
Faje, A. T. et al. High-dose glucocorticoids for the treatment of ipilimumab-induced hypophysitis is associated with reduced survival in patients with melanoma. Cancer 124, 3706–3714 (2018).
Google Scholar
Riaz, N. et al. Tumor and microenvironment evolution during immunotherapy with nivolumab. Cell 171, 934–949 (2017).
Google Scholar
Jing, Y. et al. Multi-omics prediction of immune-related adverse events during checkpoint immunotherapy. Nat. Commun. 11, 4946 (2020).
Google Scholar
Bomze, D., Hasan Ali, O., Bate, A. & Flatz, L. Association between immune-related adverse events during anti-PD-1 therapy and tumor mutational burden. JAMA Oncol. 5, 1633–1635 (2019).
Google Scholar
Yarchoan, M., Hopkins, A. & Jaffee, E. M. Tumor mutational burden and response rate to PD-1 inhibition. N. Engl. J. Med. 377, 2500–2501 (2017).
Google Scholar
Panwala, C. M., Jones, J. C. & Viney, J. L. A novel model of inflammatory bowel disease: mice deficient for the multiple drug resistance gene, mdr1a, spontaneously develop colitis. J. Immunol. 161, 5733–5744 (1998).
Google Scholar
Bausch-Fluck, D. et al. The in silico human surfaceome. Proc. Natl Acad. Sci. USA 115, E10988–E10997 (2018).
Google Scholar
Zhou, Y. et al. Intestinal toxicity to CTLA-4 blockade driven by IL-6 and myeloid infiltration. J. Exp. Med. 220, e20221333 (2023).
Google Scholar
Perez-Ruiz, E. et al. Prophylactic TNF blockade uncouples efficacy and toxicity in dual CTLA-4 and PD-1 immunotherapy. Nature 569, 428–432 (2019).
Google Scholar
Guo, X. J. et al. Interstitial pneumonitis associated with combined regimen of immunotherapy and conventional therapies—pharmacovigilance database analysis with real-world data validation. BMC Med. 21, 6 (2023).
Google Scholar
Geng, Y. et al. Effect of PD-1 inhibitor combined with X-ray irradiation on the inflammatory microenvironment and lung tissue injury in mice. J. Inflamm. Res. 15, 545–556 (2022).
Google Scholar
Salem, J. E. et al. Abatacept/ruxolitinib and screening for concomitant respiratory muscle failure to mitigate fatality of immune-checkpoint inhibitor myocarditis. Cancer Discov. 13, 1100–1115 (2023).
Google Scholar
Gupta, T. et al. Tracking in situ checkpoint inhibitor-bound target T cells in patients with checkpoint-induced colitis. Cancer Cell 42, 797–814 (2024).
Google Scholar
Lechner, M. G. et al. Inhibition of IL-17A protects against thyroid immune-related adverse events while preserving checkpoint inhibitor antitumor efficacy. J. Immunol. 209, 696–709 (2022).
Google Scholar
Li, J. et al. Remodeling of the immune and stromal cell compartment by PD-1 blockade in mismatch repair-deficient colorectal cancer. Cancer Cell 41, 1152–1169 (2023).
Google Scholar
Boles, K. S., Barchet, W., Diacovo, T., Cella, M. & Colonna, M. The tumor suppressor TSLC1/NECL-2 triggers NK-cell and CD8+ T-cell responses through the cell-surface receptor CRTAM. Blood 106, 779–786 (2005).
Google Scholar
Cortez, V. S. et al. CRTAM controls residency of gut CD4+CD8+ T cells in the steady state and maintenance of gut CD4+ Th17 during parasitic infection. J. Exp. Med. 211, 623–633 (2014).
Google Scholar
Yan, Y. et al. Multi-omic profiling highlights factors associated with resistance to immuno-chemotherapy in non-small-cell lung cancer. Nat. Genet. 57, 126–139 (2025).
Google Scholar
Ciofani, M. et al. A validated regulatory network for Th17 cell specification. Cell 151, 289–303 (2012).
Google Scholar
Mills, K. H. G. IL-17 and IL-17-producing cells in protection versus pathology. Nat. Rev. Immunol. 23, 38–54 (2023).
Google Scholar
Annunziato, F., Romagnani, C. & Romagnani, S. The 3 major types of innate and adaptive cell-mediated effector immunity. J. Allergy Clin. Immunol. 135, 626–635 (2015).
Google Scholar
Miossec, P., Korn, T. & Kuchroo, V. K. Interleukin-17 and type 17 helper T cells. N. Engl. J. Med. 361, 888–898 (2009).
Google Scholar
Saleh, M. M. & Petri, W. A. Type 3 immunity during Clostridioides difficile infection: too much of a good thing? Infect. Immun. 88, e00306-19 (2019).
Google Scholar
Yang, Z., Zhang, D., Jiang, Z., Peng, J. & Wei, H. The formidable guardian: type 3 immunity in the intestine of pigs. Virulence 15, 2424325 (2024).
Google Scholar
Tseng, W., Leong, X. & Engleman, E. Orthotopic mouse model of colorectal cancer. J. Vis. Exp. (10), 484 (2007).
Xue, G. et al. Clinical drug screening reveals clofazimine potentiates the efficacy while reducing the toxicity of anti-PD-1 and CTLA-4 immunotherapy. Cancer Cell 42, 780–796 (2024).
Google Scholar
Mellman, I., Chen, D. S., Powles, T. & Turley, S. J. The cancer–immunity cycle: indication, genotype, and immunotype. Immunity 56, 2188–2205 (2023).
Google Scholar
Ma, S. C. et al. Organ-specific metastatic landscape dissects PD-(L)1 blockade efficacy in advanced non-small cell lung cancer: applicability from clinical trials to real-world practice. BMC Med. 20, 120 (2022).
Google Scholar
Ma, S. C. et al. De novo mutation in non-tyrosine kinase domain of ROS1 as a potential predictor of immune checkpoint inhibitors in melanoma. Front. Oncol. 11, 666145 (2021).
Google Scholar
Bai, X. et al. Development and validation of a genomic mutation signature to predict response to PD-1 inhibitors in non-squamous NSCLC: a multicohort study. J. Immunother. Cancer 8, e000381 (2020).
Google Scholar
Long, L. L. et al. PARP inhibition induces synthetic lethality and adaptive immunity in LKB1-mutant lung cancer. Cancer Res. 83, 568–581 (2023).
Google Scholar
Francisco, L. M., Sage, P. T. & Sharpe, A. H. The PD-1 pathway in tolerance and autoimmunity. Immunol. Rev. 236, 219–242 (2010).
Google Scholar
Sung, C. et al. Integrative analysis of risk factors for immune-related adverse events of checkpoint blockade therapy in cancer. Nat. Cancer 4, 844–859 (2023).
Google Scholar
Axelrod, M. L. et al. T cells specific for α-myosin drive immunotherapy-related myocarditis. Nature 611, 818–826 (2022).
Google Scholar
Hailemichael, Y. et al. Interleukin-6 blockade abrogates immunotherapy toxicity and promotes tumor immunity. Cancer Cell 40, 509–523 (2022).
Google Scholar
Cervantes-Barragan, L. et al. CRTAM protects against intestinal dysbiosis during pathogenic parasitic infection by enabling Th17 maturation. Front. Immunol. 10, 1423 (2019).
Google Scholar
Ju, M. et al. Prophylactic IL-23 blockade uncouples efficacy and toxicity in dual CTLA-4 and PD-1 immunotherapy. J. Immunother. Cancer 12, e009345 (2024).
Google Scholar
Peng, S. et al. CRB1-associated retinal degeneration is dependent on bacterial translocation from the gut. Cell 187, 1387–1401 (2024).
Google Scholar
Schnell, A. et al. Targeting PGLYRP1 promotes antitumor immunity while inhibiting autoimmune neuroinflammation. Nat. Immunol. 24, 1908–1920 (2023).
Google Scholar
Hiam-Galvez, K. J., Allen, B. M. & Spitzer, M. H. Systemic immunity in cancer. Nat. Rev. Cancer 21, 345–359 (2021).
Google Scholar
Kao, C. J. et al. Immune-related events in individuals with solid tumors on immunotherapy associate with Th17 and Th2 signatures. J. Clin. Invest. 134, e176567 (2024).
Google Scholar
Kim, S. T. et al. Distinct molecular and immune hallmarks of inflammatory arthritis induced by immune checkpoint inhibitors for cancer therapy. Nat. Commun. 13, 1970 (2022).
Google Scholar
Ramírez-Ramírez, D. et al. CRTAM+ NK cells endowed with suppressor properties arise in leukemic bone marrow. J. Leukoc. Biol. 105, 999–1013 (2019).
Google Scholar
Murray, J. C. et al. Elucidating the heterogeneity of immunotherapy response and immune-related toxicities by longitudinal ctDNA and immune cell compartment tracking in lung cancer. Clin. Cancer Res. 30, 389–403 (2024).
Google Scholar
Chen, Y. et al. Spatiotemporal single-cell analysis decodes cellular dynamics underlying different responses to immunotherapy in colorectal cancer. Cancer Cell 42, 1268–1285 (2024).
Google Scholar
Zhang, L. et al. Lineage tracking reveals dynamic relationships of T cells in colorectal cancer. Nature 564, 268–272 (2018).
Google Scholar
Senent, Y., Remírez, A., Tavira, B. & Ajona, D. A mouse model to assess immunotherapy-related colitis. Methods Cell Biol. 192, 33–38 (2025).
Google Scholar
Ashcroft, T., Simpson, J. M. & Timbrell, V. Simple method of estimating severity of pulmonary fibrosis on a numerical scale. J. Clin. Pathol. 41, 467–470 (1988).
Google Scholar
Koma, Y. et al. Cell adhesion molecule 1 is a novel pancreatic-islet cell adhesion molecule that mediates nerve–islet cell interactions. Gastroenterology 134, 1544–1554 (2008).
Google Scholar
Waterhouse, A. et al. SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res. 46, W296–w303 (2018).
Google Scholar
Abanades, B., Georges, G., Bujotzek, A. & Deane, C. M. ABlooper: fast accurate antibody CDR loop structure prediction with accuracy estimation. Bioinformatics 38, 1877–1880 (2022).
Google Scholar
Dunbar, J. et al. SAbPred: a structure-based antibody prediction server. Nucleic Acids Res. 44, W474–W478 (2016).
Google Scholar
Wright, M. N., Dankowski, T. & Ziegler, A. Unbiased split variable selection for random survival forests using maximally selected rank statistics. Stat. Med. 36, 1272–1284 (2017).
Google Scholar
Yan, Y. Multi-omic profiling highlights factors associated with resistance to immuno-chemotherapy in non-small cell lung cancer. Zenodo https://doi.org/10.5281/zenodo.8227624 (2025).

