Lei, Pin-Ji, Pereira, Ethel R, Andersson, Patrik, Amoozgar, Zohreh, Van Wijnbergen, Jan Willem, O'Melia, Meghan J, Zhou, Hengbo, Chatterjee, Sampurna, Ho, William W, Posada, Jessica M, Kumar, Ashwin S, Morita, Satoru, Menzel, Lutz, Chung, Charlie, Ergin, Ilgin, Jones, Dennis, Huang, Peigen, Beyaz, Semir, Padera, Timothy P (September 2023) Cancer cell plasticity and MHC-II-mediated immune tolerance promote breast cancer metastasis to lymph nodes. Journal of Experimental Medicine, 220 (9). e20221847. ISSN 0022-1007 (Public Dataset)
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Abstract
Tumor-draining lymph nodes (TDLNs) are important for tumor antigen-specific T cell generation and effective anticancer immune responses. However, TDLNs are often the primary site of metastasis, causing immune suppression and worse outcomes. Through cross-species single-cell RNA-Seq analysis, we identified features defining cancer cell heterogeneity, plasticity, and immune evasion during breast cancer progression and lymph node metastasis (LNM). A subset of cancer cells in the lymph nodes exhibited elevated MHC class II (MHC-II) gene expression in both mice and humans. MHC-II+ cancer cells lacked costimulatory molecule expression, leading to regulatory T cell (Treg) expansion and fewer CD4+ effector T cells in TDLNs. Genetic knockout of MHC-II reduced LNM and Treg expansion, while overexpression of the MHC-II transactivator, Ciita, worsened LNM and caused excessive Treg expansion. These findings demonstrate that cancer cell MHC-II expression promotes metastasis and immune evasion in TDLNs.
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