Cathepsin S Regulates Antigen Processing and T Cell Activity in Non-Hodgkin Lymphoma

Elena Battistello, Giovanni Ciriello, George Coukos, Elie Charles Eugène Dheilly, Bruno Emanuel Ferreira De Sousa Correia, Natalya Katanayeva, Marco Mina, Elisa Oricchio, Julien Racle, Jessica Sordet-Dessimoz, Stephanie Jocelyne Sungalee, Sarah Wehrle
2020
Journal paper

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.

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