| Literature DB >> 32330455 |
Elie Dheilly1, Elena Battistello2, Natalya Katanayeva1, Stephanie Sungalee1, Justine Michaux3, Gerben Duns4, Sarah Wehrle5, Jessica Sordet-Dessimoz6, Marco Mina7, Julien Racle8, Pedro Farinha4, George Coukos3, David Gfeller8, Anja Mottok9, Robert Kridel10, Bruno E Correia11, Christian Steidl4, Michal Bassani-Sternberg3, Giovanni Ciriello7, Vincent Zoete12, Elisa Oricchio13.
Abstract
Genomic alterations in cancer cells can influence the immune system to favor tumor growth. In non-Hodgkin lymphoma, physiological interactions between B cells and the germinal center microenvironment are coopted to sustain cancer cell proliferation. We found that follicular lymphoma patients harbor a recurrent hotspot mutation targeting tyrosine 132 (Y132D) in cathepsin S (CTSS) that enhances protein activity. CTSS regulates antigen processing and CD4+ and CD8+ T cell-mediated immune responses. Loss of CTSS activity reduces lymphoma growth by limiting communication with CD4+ T follicular helper cells while inducing antigen diversification and activation of CD8+ T cells. Overall, our results suggest that CTSS inhibition has non-redundant therapeutic potential to enhance anti-tumor immune responses in indolent and aggressive lymphomas.Entities:
Keywords: T cells; antigen presentation; cysteine proteases; germinal centers; immunotherapy; lymphoma
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Year: 2020 PMID： 32330455 DOI： 10.1016/j.ccell.2020.03.016
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743