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Fucosylation of HLA-DRB1 regulates CD4+T cell-mediated anti-melanoma immunity and enhances immunotherapy efficacy: Fucose Click Chemistry

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 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.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Melanocyte

DISEASE(S): Melanoma

SUBMITTER: John Koomen

LAB HEAD: Eric Lau, PhD

PROVIDER: PXD038303 | Pride | 2022-12-16

REPOSITORIES: Pride

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			Action	DRS
	Erik_FukP0.raw	Raw
	Erik_FukP0.raw__F003553_.dta	Raw
	Erik_FukP0.raw__F003553_.mzid.gz	Mzid
	Erik_FukP0.raw__F003553_.mzid_Erik_FukP0.raw__F003553_.MGF	Mzid
	Erik_bio_ctl.raw	Raw

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

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.

2022-12-16 | PXD038068 | Pride

Fucosylation of HLA-DRB1 regulates CD4+T cell-mediated anti-melanoma immunity and enhances immunotherapy efficacy: Fucoproteomic profiling of CD4 T cells

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

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RNA-Seq of A375 cells treated with tetracycline-based crosslinking probes, with and without competition by parent tetracyclines, to show specific binding of the tetracycline analogs Col-3 and doxycycline on rRNA substructures of the human ribosome

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