Fucosylation of HLA-DRB1 regulates CD4⁺ T cell-mediated anti-melanoma immunity and enhances immunotherapy efficacy.

ABSTRACT: Immunotherapy efficacy is limited in melanoma, and combinations of immunotherapies with other modalities have yielded limited improvements but also adverse events requiring cessation of treatment. In addition to ineffective patient stratification, efficacy is impaired by paucity of intratumoral immune cells (itICs); thus, effective strategies to safely increase itICs are needed. We report that dietary administration of L-fucose induces fucosylation and cell surface enrichment of the major histocompatibility complex (MHC)-II protein HLA-DRB1 in melanoma cells, triggering CD4⁺ T cell-mediated increases in itICs and anti-tumor immunity, enhancing immune checkpoint blockade responses. Melanoma fucosylation and fucosylated HLA-DRB1 associate with intratumoral T cell abundance and ant

SUBMITTER: Lester DK 

PROVIDER: S-EPMC9970875 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature