{"doi":"10.1093/carcin/bgac064","title":"GITR agonistic stimulation enhances the anti-tumor immune response in a mouse model of ESCC","abstract":"Esophageal cancer is a significant health burden in the United States and worldwide and is the 8th leading cause of cancer-related death. Over 90% of esophageal cancers are squamous cell cancers (ESCC). Despite the development of new therapies, the overall 5-year survival rate remains lower than 20%. Recent clinical trials of immunotherapy approaches in ESCC have shown that blocking PD-1/PD-L1 interactions can reduce tumor burden and increase survival, but this only occurs in a fraction of patients. This emphasizes the need for additional therapeutic options to improve overall response rates, duration of response, and overall survival. Glucocorticoid-induced TNFR-related protein (GITR) stimulation has emerged as a promising immunotherapy target, as its stimulation appears to promote tumor regression. In this study, we evaluated the consequences of GITR agonistic stimulation with the DTA-1 antibody (anti-GITR agonist) on esophageal squamous cell carcinoma (ESCC) progression. Increased expression of GITR was observed in esophageal tumors from ESCC patients in comparison to normal adjacent tissue and in a mouse model of ESCC. 100% of mice treated with 4-NQO/IgG control antibody developed invasive squamous cell carcinoma. Less advanced esophageal tumors were seen in mice treated with 4-NQO/anti-GITR agonist compared to 4-NQO/IgG treatment. 4-NQO/anti-GITR agonist-treated mice demonstrated a significant increase in mucosal CTL/Treg ratios as well as decreased gene expression profiles of pathways related to esophageal squamous cell carcinogenesis. Thus, GITR agonism merits further study as a treatment strategy for ESCC patients.","journal":"Carcinogenesis","year":2022,"id":286544,"datarank":0.29348747745823883,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.052071790593123765,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.052071790593123765,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":4,"citers_with_citation_signal":4,"citers_with_endowment":4,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9456,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":800620,"name":"Lia Elyse Tsikretsis","orcid":null,"position":1,"is_corresponding":false},{"id":800619,"name":"Cara Alioto","orcid":null,"position":2,"is_corresponding":false},{"id":923452,"name":"Pedro Viveiros","orcid":null,"position":3,"is_corresponding":false},{"id":965854,"name":"Victoria Villaflor","orcid":"0000-0002-9111-1034","position":4,"is_corresponding":false},{"id":800142,"name":"Marie‐Pier Tétreault","orcid":"0000-0001-9071-3028","position":5,"is_corresponding":false},{"id":800618,"name":"Kelsey Wiles","orcid":null,"position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:29:52.825777Z","pmid":"35880612","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":[]}