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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 anti-programmed cell death protein 1 (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.

SUBMITTER: Lester DK

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

REPOSITORIES: biostudies-literature

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

Lester Daniel K DK Burton Chase C Gardner Alycia A Innamarato Patrick P Kodumudi Krithika K Liu Qian Q Adhikari Emma E Ming Qianqian Q Williamson Daniel B DB Frederick Dennie T DT Sharova Tatyana T White Michael G MG Markowitz Joseph J Cao Biwei B Nguyen Jonathan J Johnson Joseph J Beatty Matthew M Mockabee-Macias Andrea A Mercurio Matthew M Watson Gregory G Chen Pei-Ling PL McCarthy Susan S MoranSegura Carlos C Messina Jane J Thomas Kerry L KL Darville Lancia L Izumi Victoria V Koomen John M JM Pilon-Thomas Shari A SA Ruffell Brian B Luca Vincent C VC Haltiwanger Robert S RS Wang Xuefeng X Wargo Jennifer A JA Boland Genevieve M GM Lau Eric K EK

Nature cancer 20230123 2

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 histoc ...[more]

PMID: 36690875

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Dataset Information

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

Publications

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

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Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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