{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wang X"],"funding":["American Association of Immunologists","American Cancer Society","NIDCR NIH HHS","U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research","U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases","NIAID NIH HHS","U.S. Department of Health & Human Services | NIH | National Cancer Institute","Cancer League of Colorado","NCI NIH HHS"],"pagination":["723-734"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8027191"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["18(3)"],"pubmed_abstract":["Cancer cells can evade immune recognition by losing major histocompatibility complex (MHC) class I. Hence, MHC class I-negative cancers represent the most challenging cancers to treat. Chemotherapeutic drugs not only directly kill tumors but also modulate the tumor immune microenvironment. However, it remains unknown whether chemotherapy-treated cancer cells can activate CD8 T cells independent of tumor-derived MHC class I and whether such MHC class I-independent CD8 T-cell activation can be exploited for cancer immunotherapy. Here, we showed that chemotherapy-treated cancer cells directly activated CD8 T cells in an MHC class I-independent manner and that these activated CD8 T cells exhibit virtual memory (VM) phenotypes. Consistently, in vivo chemotherapeutic treatment preferentially increased tumor-infiltrating VM CD8 T cells. Mechanistically, MHC class I-independent activation of CD8 T cells requires cell-cell contact and activation of the PI3K pathway. VM CD8 T cells contribute to a superior therapeutic effect on MHC class I-deficient tumors. Using humanized mouse models or primary human CD8 T cells, we also demonstrated that chemotherapy-treated human lymphomas activated VM CD8 T cells independent of tumor-derived MHC class I. In conclusion, CD8 T cells can be directly activated in an MHC class I-independent manner by chemotherapy-treated cancers, and these activated CD8 T cells may be exploited for developing new strategies to treat MHC class I-deficient cancers."],"journal":["Cellular & molecular immunology"],"pubmed_title":["MHC class I-independent activation of virtual memory CD8 T cells induced by chemotherapeutic agent-treated cancer cells."],"pmcid":["PMC8027191"],"funding_grant_id":["R01-CA229174","F31DE027854","R21 CA184707","ACS IRG #16-184-56","R01 CA166325","R21-AI110777","T32 AI007405","R01-CA166325","Careers in Immunology Fellowship","R21 AI133110","R01 CA229174","R21 AI110777","R21-AI133110","R21-CA184707","F31 DE027854"],"pubmed_authors":["Chen SMY","Waschke BC","Chen Z","Wang JH","Wang X","Woolaver RA"],"additional_accession":[]},"is_claimable":false,"name":"MHC class I-independent activation of virtual memory CD8 T cells induced by chemotherapeutic agent-treated cancer cells.","description":"Cancer cells can evade immune recognition by losing major histocompatibility complex (MHC) class I. Hence, MHC class I-negative cancers represent the most challenging cancers to treat. Chemotherapeutic drugs not only directly kill tumors but also modulate the tumor immune microenvironment. However, it remains unknown whether chemotherapy-treated cancer cells can activate CD8 T cells independent of tumor-derived MHC class I and whether such MHC class I-independent CD8 T-cell activation can be exploited for cancer immunotherapy. Here, we showed that chemotherapy-treated cancer cells directly activated CD8 T cells in an MHC class I-independent manner and that these activated CD8 T cells exhibit virtual memory (VM) phenotypes. Consistently, in vivo chemotherapeutic treatment preferentially increased tumor-infiltrating VM CD8 T cells. Mechanistically, MHC class I-independent activation of CD8 T cells requires cell-cell contact and activation of the PI3K pathway. VM CD8 T cells contribute to a superior therapeutic effect on MHC class I-deficient tumors. Using humanized mouse models or primary human CD8 T cells, we also demonstrated that chemotherapy-treated human lymphomas activated VM CD8 T cells independent of tumor-derived MHC class I. In conclusion, CD8 T cells can be directly activated in an MHC class I-independent manner by chemotherapy-treated cancers, and these activated CD8 T cells may be exploited for developing new strategies to treat MHC class I-deficient cancers.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Mar","modification":"2025-04-27T01:42:50.024Z","creation":"2025-04-06T18:21:25.416Z"},"accession":"S-EPMC8027191","cross_references":{"pubmed":["32427883"],"doi":["10.1038/s41423-020-0463-2"]}}