Dataset Information

Microbe-Mediated Activation of Toll-like Receptor 2 Drives PDL1 Expression in HNSCC.

ABSTRACT: As immunotherapies targeting the PDL1 checkpoint have become a mainstay of treatment for a subset of head and neck squamous cell carcinoma (HNSCC) patients, a detailed understanding of the mechanisms underlying PDL1-mediated immune evasion is needed. To elucidate factors regulating expression of PDL1 in HNSCC cells, a genome-wide CRISPR profiling approach was implemented to identify genes and pathways conferring altered PDL1 expression in an HNSCC cell line model. Our screen nominated several candidate PDL1 drivers, including Toll-like Receptor 2 (TLR2). Depletion of TLR2 blocks interferon-γ-induced PDL1 expression, and stimulation of TLR2 with either Staphylococcus aureus or a bacterial lipopeptide mimetic, Pam3CSK4, enhanced PDL1 expression in multiple models. The data herein demonstrate a role for TLR2 in modulating the expression of PDL1 in HNSCC models and suggest that microbiota may directly modulate immunosuppression in cancer cells. Our study represents a step toward disentangling the diverse pathways and stimuli regulating PDL1 expression in HNSCC and underscores a need for future work to characterize the complex microbiome in HNSCC patients treated with immunotherapy.

SUBMITTER: Mann JE

PROVIDER: S-EPMC8508280 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Microbe-Mediated Activation of Toll-like Receptor 2 Drives PDL1 Expression in HNSCC.

Mann Jacqueline E JE Ludwig Megan L ML Kulkarni Aditi A Scheftz Erin B EB Murray Isabel R IR Zhai Jingyi J Gensterblum-Miller Elizabeth E Jiang Hui H Brenner J Chad JC

Cancers 20210924 19

As immunotherapies targeting the PDL1 checkpoint have become a mainstay of treatment for a subset of head and neck squamous cell carcinoma (HNSCC) patients, a detailed understanding of the mechanisms underlying PDL1-mediated immune evasion is needed. To elucidate factors regulating expression of PDL1 in HNSCC cells, a genome-wide CRISPR profiling approach was implemented to identify genes and pathways conferring altered PDL1 expression in an HNSCC cell line model. Our screen nominated several ca ...[more]

PMID: 34638266

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Dataset Information

Microbe-Mediated Activation of Toll-like Receptor 2 Drives PDL1 Expression in HNSCC.

Publications

Microbe-Mediated Activation of Toll-like Receptor 2 Drives PDL1 Expression in HNSCC.

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