Nicolas Manel

Nicolas Manel, PhD is Research Director at INSERM and Head of the Immunity and Cancer Laboratory at Institut Curie, Paris. His group has made foundational contributions to understanding how cancer cells evade cytotoxic T lymphocyte recognition through defects in the MHC class I antigen presentation pathway. His laboratory characterized the molecular consequences of beta-2 microglobulin (B2M) biallelic loss in tumors, demonstrating that B2M inactivation leads to complete abrogation of surface MHC-I expression and renders tumors invisible to CD8+ T cells, constituting one of the most prevalent mechanisms of acquired resistance to PD-1/CTLA-4 checkpoint immunotherapy. His work elucidated how B2M loss co-occurs with tumor mutational burden and neoantigen load, creating a paradox where high-neoantigen tumors can escape via antigen presentation defects rather than neoantigen depletion. He also pioneered the concept that cGAS-STING pathway activation in tumor cells can restore MHC-I expression and partially overcome B2M-independent antigen presentation defects. Dr. Manel's research on the interplay between innate immune sensing and adaptive immune recognition has opened new therapeutic avenues for restoring MHC-I in immunotherapy-resistant cancers.