Cancers, Vol. 13, Pages 4782: Microbe-Mediated Activation of Toll-like Receptor 2 Drives PDL1 Expression in HNSCC

Cancers, Vol. 13, Pages 4782: Microbe-Mediated Activation of Toll-like Receptor 2 Drives PDL1 Expression in HNSCC Cancers doi: 10.3390/cancers13194782 Authors: Jacqueline E Mann Megan L Ludwig Aditi Kulkarni Erin B Scheftz Isabel R Murray Jingyi Zhai Elizabeth Gensterblum-Miller Hui Jiang J Chad Brenner 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 t...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research