Cancer cell plasticity and MHC-II–mediated immune tolerance promote breast cancer metastasis to lymph nodes
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jem_20221847.pdf
Description
Published version
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9.07 MB
Format
Adobe PDF
Checksum (MD5)
b96ce9d9fc8e386e41272c3907ec4366
Author(s)
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
Date Issued
September 4, 2023
Journal
Journal of Experimental Medicine
Publisher
Rockefeller University Press
Citation
Pin-Ji Lei, Ethel R. Pereira, Patrik Andersson, Zohreh Amoozgar, Jan Willem Van Wijnbergen, Meghan J. O’Melia, Hengbo Zhou, Sampurna Chatterjee, William W. Ho, Jessica M. Posada, Ashwin S. Kumar, Satoru Morita, Lutz Menzel, Charlie Chung, Ilgin Ergin, Dennis Jones, Peigen Huang, Semir Beyaz, Timothy P. Padera; Cancer cell plasticity and MHC-II–mediated immune tolerance promote breast cancer metastasis to lymph nodes. J Exp Med 4 September 2023; 220 (9): e20221847.
Version
Final published version
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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DOI of Published Version
https://doi.org/10.1084/jem.20221847
