{"doi":"10.3390/cancers13194782","title":"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.","journal":"Cancers","year":2021,"id":185744,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9475,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":590383,"name":"Megan Ludwig","orcid":"0000-0003-3133-3679","position":1,"is_corresponding":false},{"id":449665,"name":"Aditi Kulkarni","orcid":"0000-0002-4886-6095","position":2,"is_corresponding":false},{"id":742934,"name":"Erin B. Scheftz","orcid":null,"position":3,"is_corresponding":false},{"id":742935,"name":"Isabel R. Murray","orcid":null,"position":4,"is_corresponding":false},{"id":263704,"name":"Jingyi Zhai","orcid":"0000-0003-0475-8786","position":5,"is_corresponding":false},{"id":741929,"name":"Elizabeth Gensterblum‐Miller","orcid":"0000-0002-8714-1257","position":6,"is_corresponding":false},{"id":263708,"name":"Hui Jiang","orcid":"0000-0003-2718-9811","position":7,"is_corresponding":false},{"id":376564,"name":"J. Chad Brenner","orcid":"0000-0003-3238-1111","position":8,"is_corresponding":false},{"id":742933,"name":"Jacqueline E. Mann","orcid":null,"position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-18T23:48:38.805613Z","pmid":"34638266","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}