{"doi":"10.1016/j.esmoop.2024.102942","title":"Viewing the immune checkpoint VISTA: landscape and outcomes across cancers","abstract":"BACKGROUND: Optimizing immune checkpoint inhibitor (ICI) therapy may require identification of co-targetable checkpoint pathways via immune profiling. Herein, we analyzed the transcriptomic expression and clinical correlates of V-domain immunoglobulin suppressor of T-cell activation (VISTA), a promising targetable checkpoint. PATIENTS AND METHODS: RNA sequencing was carried out on 514 tissues reflecting diverse advanced/metastatic cancers. Expression of eight immune checkpoint markers [lymphocyte-activation gene 3 (LAG-3), tumor necrosis factor receptor superfamily 14 (TNFRSF14), programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), programmed death-ligand 2 (PD-L2), B- and T-lymphocyte attenuator (BTLA), T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), cytotoxic T-lymphocyte antigen 4 (CTLA-4)], in addition to VISTA, was analyzed, along with clinical outcomes. RESULTS: High VISTA RNA expression was observed in 32% of tumors (66/514) and was the most common highly expressed checkpoint among the nine assessed. High VISTA expression was independently correlated with high BTLA, TIM-3, and TNFRSF14, and with a diagnosis of pancreatic, small intestine, and stomach cancer. VISTA transcript levels did not correlate with overall survival (OS) from metastatic/advanced disease in the pan-cancer cohort or with immunotherapy outcome (progression-free survival and OS from the start of ICI) in 217 ICI-treated patients. However, in ICI-treated pancreatic cancer patients (n = 16), median OS was significantly shorter (from immunotherapy initiation) for the high- versus not-high-VISTA groups (0.28 versus 1.21 years) (P = 0.047); in contrast, VISTA levels were not correlated with OS in 36 pancreatic cancer patients who did not receive ICI. CONCLUSION: High VISTA expression correlates with high BTLA, TIM-3, and TNFRSF14 checkpoint-related molecules and with poorer post-immunotherapy survival in pancreatic cancer, consistent with prior literature indicating that VISTA is prominently expressed on CD68+ macrophages in pancreatic cancers and requiring validation in larger prospective studies. Immunomic analysis may be important for individualized precision immunotherapy.","journal":"ESMO Open","year":2024,"id":421065,"datarank":0.5244761342199721,"base_score":3.4965075614664802,"endowment":3.4965075614664802,"self_citation_contribution":0.5244761342199721,"citation_network_contribution":0.0,"self_endowment_contribution":0.5244761342199721,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":32,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8238,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":108759,"name":"Razelle Kurzrock","orcid":"0000-0003-4110-1214","position":1,"is_corresponding":false},{"id":1055331,"name":"Hirotaka Miyashita","orcid":"0000-0002-0433-9779","position":2,"is_corresponding":false},{"id":235241,"name":"Jacob J. Adashek","orcid":"0000-0003-4272-312X","position":3,"is_corresponding":false},{"id":235243,"name":"Suzanna Lee","orcid":"0000-0002-9502-4907","position":4,"is_corresponding":false},{"id":108758,"name":"Mina Nikanjam","orcid":"0000-0001-7052-6348","position":5,"is_corresponding":false},{"id":235234,"name":"Ramez N. Eskander","orcid":"0000-0002-2101-1935","position":6,"is_corresponding":false},{"id":640681,"name":"Hitendra Patel","orcid":"0000-0001-8746-2600","position":7,"is_corresponding":false},{"id":1213920,"name":"G.P. Botta","orcid":null,"position":8,"is_corresponding":false},{"id":1055333,"name":"Mary Nesline","orcid":"0000-0003-0523-4597","position":9,"is_corresponding":false},{"id":1055332,"name":"Sarabjot Pabla","orcid":"0000-0002-7746-9144","position":10,"is_corresponding":false},{"id":322907,"name":"Jeffrey M. Conroy","orcid":"0000-0003-1764-9706","position":11,"is_corresponding":false},{"id":1055334,"name":"Paul DePietro","orcid":"0000-0001-9072-0631","position":12,"is_corresponding":false},{"id":235244,"name":"Jason K. Sicklick","orcid":"0000-0003-4403-0271","position":13,"is_corresponding":false},{"id":235228,"name":"Shumei Kato","orcid":"0000-0003-1193-1815","position":14,"is_corresponding":false},{"id":1055330,"name":"Daisuke Nishizaki","orcid":"0000-0002-6746-3224","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:57:36.298171Z","pmid":"38503143","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":[]}