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PD-L1 AND ICOSL DISCRIMINATE HUMAN SECRETORY AND HELPER DENDRITIC CELLS IN CANCER, ALLERGY AND AUTOIMMUNITY

ABSTRACT: In this study, we define a novel phenotypic and functional dichotomy of human dendritic cells (DC), with strong relevance to cancer, allergy, and autoimmunity. Using 16 different stimuli in vitro (130 observations), we describe two states of human activated DC. PD-L1highICOSLlow Secretory DC produced large amounts of inflammatory cytokines and chemokines but induced very low levels of T helper (Th) cytokines following DC-T co-culture; conversely PD-L1lowICOSLhigh Helper DC produced low levels of secreted factors but induced high levels and a broad range of Th cytokines. Secretory DC were aligned with mature migratory LAMP3+ DC in three different cancer types, atopic dermatitis, and lupus nephritis by single-cell transcriptomics. They were associated with T cell inflammation, overexpressed stimulatory and inhibitory checkpoints, acquired increased cell-cell communication, and were associated with good prognosis in head and neck squamous cell carcinoma, and with response to checkpoint blockade in Melanoma. This functional dichotomy of DC has broad implications in inflammation and immunotherapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE169381 | GEO | 2022/01/01

REPOSITORIES: GEO

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