{"doi":"10.1038/s42003-021-02522-2","title":"Distinct immune microenvironment profiles of therapeutic responders emerge in combined TGFβ/PD-L1 blockade-treated squamous cell carcinoma","abstract":"Abstract Transforming growth factor beta (TGFβ) and programmed death-ligand 1 (PD-L1) are often overproduced in refractory squamous cell carcinoma (SCC). We examined spatial patterns of PD-L1 + cells in mouse and human SCCs and found that PD-L1 was primarily expressed on infiltrating leukocytes. Although combined TGFβ and PD-L1 blockade are undergoing cancer clinical trials, there are no predictive markers for therapeutic responders. To address this, we used both a small molecule TGFβ inhibitor in combination with anti-PD-L1 and a bifunctional fusion protein targeting both TGFβ and PD-L1 to treat mouse SCCs and found TGFβ inhibition enhanced PD-L1 blockade-induced tumor eradication in multiple tumor models. Furthermore, we identified distinct cell populations of responders and non-responders to bintrafusp alfa, with responders showing a shift toward a more immune-permissive microenvironment. The cellular and molecular signatures of responders versus non-responders to combined TGFβ and PD-L1 blockade provide important insights into future personalized immunotherapy in SCC.","journal":"Communications Biology","year":2021,"id":176641,"datarank":0.4636563680037475,"base_score":3.091042453358316,"endowment":3.091042453358316,"self_citation_contribution":0.4636563680037475,"citation_network_contribution":0.0,"self_endowment_contribution":0.4636563680037475,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9558,"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":282853,"name":"Rachel A. Woolaver","orcid":"0000-0002-8107-599X","position":1,"is_corresponding":false},{"id":689092,"name":"Spencer C. Hall","orcid":"0000-0001-6783-2344","position":2,"is_corresponding":false},{"id":33618,"name":"Christian D. Young","orcid":"0000-0001-9846-488X","position":3,"is_corresponding":false},{"id":11003,"name":"Sana D. Karam","orcid":"0000-0003-1676-5967","position":4,"is_corresponding":false},{"id":28359,"name":"Antonio Jimeno","orcid":"0000-0001-8560-0440","position":5,"is_corresponding":false},{"id":625956,"name":"Yan Lan","orcid":"0000-0002-5850-9737","position":6,"is_corresponding":false},{"id":28361,"name":"David Raben","orcid":null,"position":7,"is_corresponding":false},{"id":282855,"name":"Jing Wang","orcid":"0000-0003-4343-2527","position":8,"is_corresponding":false},{"id":241420,"name":"Xiao‐Jing Wang","orcid":"0000-0001-8695-7361","position":9,"is_corresponding":false},{"id":397919,"name":"Alexander A. Strait","orcid":"0000-0003-2397-8311","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:47:23.605867Z","pmid":"34433873","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":[]}