{"doi":"10.4143/crt.2025.126","title":"Clinicopathological Factors Influencing PD-L1 Expression and the Effect of Immune Checkpoint Inhibitors on Survival Outcomes in Patients with Gastric Cancer Depending on Sex in a Tertiary Hospital in South Korea","abstract":"Purpose: Programmed cell death ligand-1 (PD-L1) negatively regulates T-cell activation, and exhibits sex-based differences in expression and immune responses. This study investigated sex-related differences in clinicopathological factors influencing PD-L1 expression and the effect of immune checkpoint inhibitors (ICIs) on survival in gastric cancer (GC) patients in South Korea. Materials and Methods: We analyzed a prospective cohort of 468 GC patients who underwent PD-L1 immunohistochemistry. Age, tumor characteristics, molecular features, and survival outcomes were compared by sex. Multivariate analyses, including Cox proportional hazards modeling with an interaction term for sex, were performed. Results: Among 468 patients, 280 (59.8%) were PD-L1 positive. In the overall cohort, PD-L1 positivity was significantly associated with Epstein-BarrVirus (EBV) infection (odd ratio [OR]=7.46, p<0.001), antral location of GC (OR=1.84, p=0.027), and macrosatellite instability-High (MSI-H) (OR=5.04, p=0.027). Diffuse-type histology was inversely associated (OR=0.22, p=0.041). In males, EBV (OR=36.27) and antral location (OR=2.38) were significant. In females, only MSI-H was significant (OR=11.63). ICI-containing therapy significantly improved survival in males (p=0.012) but not in females (p=0.415). Cox regression showed a survival benefit from ICIs (HR=0.70, p=0.080), with a borderline-significant interaction by sex (p=0.073). Conclusion: PD-L1 expression and therapeutic efficacy of ICIs differ by sex in GC. EBV infection and antral tumor location were independent factors in males, while MSI-H status was significant in females. These findings highlights the importance of sex-based immunobiology in tailoring GC treatment strategies.","journal":"Cancer Research and Treatment","year":2025,"id":534423,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9603,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":390686,"name":"Nayoung Kim","orcid":"0000-0002-9397-0406","position":1,"is_corresponding":false},{"id":458796,"name":"Ji‐Hyun Kim","orcid":"0000-0002-7040-7397","position":2,"is_corresponding":false},{"id":1417020,"name":"Hyeon Jeong Oh","orcid":"0000-0002-9998-3988","position":3,"is_corresponding":false},{"id":1417567,"name":"Yeejin Kim","orcid":null,"position":4,"is_corresponding":false},{"id":1417021,"name":"Yonghoon Choi","orcid":"0000-0002-1331-969X","position":5,"is_corresponding":false},{"id":1417022,"name":"Hyemin Jo","orcid":"0009-0002-8829-2994","position":6,"is_corresponding":false},{"id":1417568,"name":"Ho-Kyoung Lee","orcid":null,"position":7,"is_corresponding":false},{"id":1417023,"name":"Jinju Choi","orcid":"0000-0002-0869-898X","position":8,"is_corresponding":false},{"id":1417024,"name":"Yu Kyung Jun","orcid":"0000-0002-4046-8578","position":9,"is_corresponding":false},{"id":244884,"name":"Hyuk Yoon","orcid":"0000-0002-2657-0349","position":10,"is_corresponding":false},{"id":390684,"name":"Cheol Min Shin","orcid":"0000-0003-2265-9845","position":11,"is_corresponding":false},{"id":390685,"name":"Young Soo Park","orcid":"0000-0003-1893-7726","position":12,"is_corresponding":false},{"id":390687,"name":"Dong Ho Lee","orcid":"0000-0002-6376-410X","position":13,"is_corresponding":false},{"id":600845,"name":"Hye Seung Lee","orcid":"0000-0002-1667-7986","position":14,"is_corresponding":false},{"id":1417025,"name":"So Hyun Kang","orcid":"0000-0002-8248-9043","position":15,"is_corresponding":false},{"id":1417026,"name":"Young Suk Park","orcid":"0000-0002-6352-9759","position":16,"is_corresponding":false},{"id":1417027,"name":"Sang-Hoon Ahn","orcid":"0000-0001-8827-3625","position":17,"is_corresponding":false},{"id":623908,"name":"Yun‐Suhk Suh","orcid":"0000-0003-3319-8482","position":18,"is_corresponding":false},{"id":1021471,"name":"Do Joong Park","orcid":"0000-0001-9644-6127","position":19,"is_corresponding":false},{"id":1417028,"name":"Hyung‐Ho Kim","orcid":"0000-0002-8916-0048","position":20,"is_corresponding":false},{"id":809447,"name":"Ji‐Won Kim","orcid":"0000-0001-6426-9074","position":21,"is_corresponding":false},{"id":1417029,"name":"Jin Won Kim","orcid":"0000-0002-1357-7015","position":22,"is_corresponding":false},{"id":631570,"name":"Keun-Wook Lee","orcid":null,"position":23,"is_corresponding":false},{"id":1417030,"name":"Won Ick Chang","orcid":"0000-0002-5268-290X","position":24,"is_corresponding":false},{"id":1417031,"name":"Yoon Jin Lee","orcid":"0000-0002-3572-029X","position":25,"is_corresponding":false},{"id":1417032,"name":"Kyoung Ho Lee","orcid":"0000-0001-6045-765X","position":26,"is_corresponding":false},{"id":1417033,"name":"Young Hoon Kim","orcid":"0000-0001-5554-3828","position":27,"is_corresponding":false},{"id":1417034,"name":"Soyeon Ahn","orcid":"0000-0003-3440-2027","position":28,"is_corresponding":false},{"id":1417019,"name":"Jeong Hwan Lee","orcid":"0009-0003-6986-5723","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:51:47.434742Z","pmid":"40808532","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":[]}