{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:59:59Z","timestamp":1790315999471,"version":"4.1.0"},"reference-count":97,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Immune checkpoint inhibitor (ICI)-based neoadjuvant\/perioperative strategies are expanding for locally advanced resectable gastric\/gastroesophageal junction (G\/GEJ) adenocarcinoma, but the evidence base differs substantially across strategies, and improved pathological response has not consistently translated into survival benefit. We aimed to synthesize strategy-specific comparative and prospective single-arm evidence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PubMed, Web of Science, Embase, the Cochrane Library, and major oncology conference proceedings were searched from inception to August 3, 2026. RCTs and prospective single-arm trials evaluating ICI-containing treatment initiated before surgery were included. Five strategies were evaluated: ICI plus chemotherapy (ICI+CT), ICI plus chemotherapy and anti-angiogenic therapy (ICI+CT+A), ICI plus chemoradiotherapy (ICI+CRT), ICI plus chemotherapy and anti-HER2 therapy (ICI+CT+H), and dual-ICI therapy (ICI+ICI). Random-effects comparative meta-analyses were conducted separately by strategy, while single-arm analyses provided descriptive absolute estimates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 74 trials, including 16 RCTs and 58 prospective single-arm trials, were included. In randomized comparisons, ICI+CT was associated with improved pCR (RR, 3.01; 95% CI, 2.19-4.15) and MPR (RR, 1.59; 95% CI, 1.36-1.85) and, in perioperative trials, OS (HR, 0.81; 95% CI, 0.70-0.93) and EFS (HR, 0.74; 95% CI, 0.66-0.83) compared with chemotherapy. ICI+CT+A was associated with improved pCR (RR, 3.43; 95% CI, 1.85-6.37) and MPR (RR, 1.40; 95% CI, 1.12-1.76), but survival evidence was limited to one phase II RCT reporting OS. Comparative evidence for ICI+CRT was limited to one small RCT. Evidence for ICI+CT+H and ICI+ICI was derived mainly from small biomarker-selected noncomparative studies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Evidence differed substantially across the five strategies. ICI+CT was associated with improved pCR and MPR and, in perioperative RCTs, OS and EFS; it had the largest and most mature randomized evidence base. ICI+CT+A was associated with improved pCR and MPR, whereas comparative evidence for ICI+CRT, ICI+CT+H, and ICI+ICI remained limited. Further comparative trials are required, particularly for safety and long-term survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420251271789<\/jats:ext-link>\n                      , identifier CRD420251271789.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1909466","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:33:05Z","timestamp":1790314385000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of immune checkpoint inhibitors as neoadjuvant\/perioperative therapy for locally advanced resectable gastric\/gastroesophageal junction adenocarcinoma: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhengyi","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Shenzhen People\u2019s Hospital, The Second Clinical Medical College, Jinan University","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[{"name":"The Fourth School of Clinical Medicine, Guangzhou University of Chinese Medicine","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanling","family":"Sun","sequence":"additional","affiliation":[{"name":"Shenzhen College of Clinical Medicine, Guangzhou University of Chinese Medicine","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nini","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shenzhen People\u2019s Hospital, The Second Clinical Medical College, Jinan University","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junlin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Shenzhen College of Clinical Medicine, Guangzhou University of Chinese Medicine","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihan","family":"Chen","sequence":"additional","affiliation":[{"name":"Shenzhen College of Clinical Medicine, Guangzhou University of Chinese Medicine","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shenzhen People\u2019s Hospital (the Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology)","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shenzhen People\u2019s Hospital (the Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology)","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2026.02.003","article-title":"Nivolumab plus chemotherapy as first-line treatment for advanced gastric, gastroesophageal junction, and esophageal 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