{"doi":"10.1136/jitc-2023-007463","title":"Immune microenvironment of basal cell carcinoma and tumor regression following combined PD-1/LAG-3 blockade","abstract":"Systemic treatment options for patients with locally advanced or metastatic basal cell carcinoma (BCC) are limited, particularly when tumors are refractory to anti-programmed cell death protein-1 (PD-1). A better understanding of immune checkpoint expression within the BCC tumor microenvironment may inform combinatorial treatment strategies to optimize response rates. CD3, PD-1, programmed death ligand-1 (PD-L1), lymphocyte activation gene 3 (LAG-3), and T-cell immunoglobulin domain and mucin domain 3 (TIM-3)+ cell densities within the tumor microenvironment of 34 archival, histologically aggressive BCCs were assessed. Tumor infiltrating lymphocyte (TIL) expression of PD-1, PD-L1, and LAG-3, and to a lesser degree TIM-3, correlated with increasing CD3+ T-cell densities (Pearson’s r =0.89, 0.72, 0.87, and 0.63, respectively). 100% of BCCs (34/34) demonstrated LAG-3 and PD-1 expression in >1% TIL; and the correlation between PD-1 and LAG-3 densities was high (Pearson’s r=0.89). LAG-3 was expressed at ~50% of the level of PD-1. Additionally, we present a patient with locally-advanced BCC who experienced stable disease during and after 45 weeks of first-line anti-PD-1 (nivolumab), followed by a partial response after the addition of anti-LAG-3 (relatlimab). Longitudinal biopsies throughout the treatment course showed a graduated increase in LAG-3 expression after anti-PD-1 therapy, lending support for coordinated immunosuppression and suggesting LAG-3 as a co-target for combination therapy to augment the clinical impact of anti-PD-(L)1.","journal":"Journal for ImmunoTherapy of Cancer","year":2023,"id":361502,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9521,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":240446,"name":"Jonathan R. Lai","orcid":"0000-0002-4863-0015","position":1,"is_corresponding":false},{"id":959515,"name":"Kara M. Schenk","orcid":"0000-0001-5147-8301","position":2,"is_corresponding":false},{"id":1114252,"name":"Abha Soni","orcid":null,"position":3,"is_corresponding":false},{"id":1097873,"name":"Elizabeth Will","orcid":"0000-0002-4152-1166","position":4,"is_corresponding":false},{"id":1114253,"name":"Logan L Engle","orcid":null,"position":5,"is_corresponding":false},{"id":624572,"name":"Haiying Xu","orcid":null,"position":6,"is_corresponding":false},{"id":1114254,"name":"Alexandra Ogurtsova","orcid":null,"position":7,"is_corresponding":false},{"id":1114255,"name":"Vrinda Madan","orcid":null,"position":8,"is_corresponding":false},{"id":1114256,"name":"Jennifer K Chong","orcid":null,"position":9,"is_corresponding":false},{"id":254625,"name":"Daphne Wang","orcid":"0000-0002-7202-8075","position":10,"is_corresponding":false},{"id":94797,"name":"B. Green","orcid":null,"position":11,"is_corresponding":false},{"id":413436,"name":"Peter Nguyen","orcid":"0000-0002-1419-5975","position":12,"is_corresponding":false},{"id":1113774,"name":"Megan D. Schollenberger","orcid":"0000-0002-6114-090X","position":13,"is_corresponding":false},{"id":258581,"name":"Evan J. Lipson","orcid":"0000-0003-2976-0911","position":14,"is_corresponding":false},{"id":59435,"name":"Janis M. Taube","orcid":"0000-0002-8273-4395","position":15,"is_corresponding":false},{"id":1016560,"name":"Julie S. Deutsch","orcid":"0000-0002-8040-5205","position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-19T01:14:10.680991Z","pmid":"38101862","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":[]}