{"doi":"10.18632/oncotarget.27348","title":"Lactate induces PD-L1 in HRASG12V-positive oropharyngeal squamous cell carcinoma","abstract":"// Alexander K. Verma 1 , Shanta M. Messerli 1 and W. Keith Miskimins 1 1 Cancer Biology and Immunotherapies Group, Sanford Research, Sioux Falls, SD, USA Correspondence to: W. Keith Miskimins, email: Keith.Miskimins@sanfordhealth.org Keywords: oropharyngeal cancer; lactate; Ras; anti-tumor immunity; PD-L1 Received: January 10, 2019     Accepted: November 13, 2019     Published: April 28, 2020 ABSTRACT Intratumoral lactate production negatively correlates with survival and tumor clearance in the setting of human papillomavirus positive oropharyngeal squamous cell carcinoma (HPV-positive OPSCC). Robust anti-tumor immune activity is required for tumor clearance in human patients and animal models of this disease, and intratumoral lactate interferes with this process. While lactate is known to directly inhibit T cell activity, recent evidence has demonstrated that lactate can affect gene expression in multiple cell types. We therefore sought to determine if lactate in the tumor microenvironment could aid immune evasion by inducing the expression of immune checkpoint co-inhibitors. Using a mouse cell line transformed with HPV16 E6, E7, and HRAS G12V , we determined that OPSCC cells carrying the HRAS G12V mutant showed significantly increased expression of PD-L1 in the presence of extracellular lactate. Furthermore, we demonstrate here that lactate activates the MEK/ERK pathway in Ras-mutated cells.","journal":"Oncotarget","year":2020,"id":107225,"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":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9523,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":485925,"name":"Shanta M. Messerli","orcid":null,"position":1,"is_corresponding":false},{"id":485267,"name":"W. Keith Miskimins","orcid":"0000-0001-9950-7351","position":2,"is_corresponding":false},{"id":516875,"name":"Alexander K. Verma","orcid":null,"position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-18T23:12:34.898963Z","pmid":"32391119","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":[]}