Innate immune checkpoint inhibitor resistance is associated with melanoma sub-types exhibiting invasive and de-differentiated gene expression signatures
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE213145 | GEO | 2022/09/15
REPOSITORIES: GEO
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Project description: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 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 anti-PD1 responder status in patient melanoma specimens, suggesting the potential use of melanoma fucosylation as a strategy for stratifying patients for immunotherapies. Our findings demonstrate that fucosylation is a key mediator of anti-tumor immunity, and importantly, suggest that L-fucose is a powerful agent for safely increasing ItICs and immunotherapy efficacy in melanoma.
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