Publication
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.
Didier Trono, Priscilla Turelli, Evaristo Jose Planet Letschert, Filipe Amândio Brandão Sanches Vong Martins, Florian Huber, Olga Marie Louise Rosspopoff, Romain Forey, Sandra Eloise Kjeldsen, Cyril David Son-Tuyên Pulver, Joana Carlevaro Fita