{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T12:48:03Z","timestamp":1785847683166,"version":"3.56.0"},"reference-count":8,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"unspecified","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010018","name":"Doctoral Startup Foundation of Liaoning Province","doi-asserted-by":"crossref","award":["2024-BSLH-154"],"award-info":[{"award-number":["2024-BSLH-154"]}],"id":[{"id":"10.13039\/501100010018","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Key R&D Project of Liaoning Provincial Science and Technology Program","award":["2025JH2\/101800145"],"award-info":[{"award-number":["2025JH2\/101800145"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,7,25]]},"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:p>Gastric cancer (GC) remains a major clinical challenge, with most patients exhibiting primary resistance to anti-programmed cell death protein-1 (anti-PD-1) immunotherapy and a lack of effective predictive biomarkers. Most advanced GC presents as immune-excluded \u201ccold\u201d tumors that respond poorly to immune checkpoint blockade. Traditional Chinese medicine (TCM) \u201cYong (abscess)\u201d syndrome and the \u201ctreating GC as Yong\u201d theory are widely applied in clinical practice, yet lack clear molecular and immunological mechanisms. Here, by translating these clinical observations into modern biological terms, we present an original, testable hypothesis proposing the \u201cYong\u201d syndrome\u2013cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) axis as the central molecular bridge connecting TCM syndrome subtypes, GC histological subtypes, and TME reprogramming. We hypothesize that heat-clearing and blood-activating TCM monomers activate cGAS-STING in a subtype-selective manner to convert \u201ccold\u201d tumors to \u201chot\u201d immunogenic phenotypes, directly addressing the critical clinical dilemmas of primary anti-PD-1 resistance and insufficient biomarkers in GC immunotherapy. This hypothesis translates universal cGAS-STING mechanisms into a clinically actionable, syndrome-based precision strategy for GC.<\/jats:p>","DOI":"10.1136\/jitc-2026-015810","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T12:10:37Z","timestamp":1785845437000},"page":"e015810","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["\u201cYong\u201d syndrome\u2013cGAS-STING axis: a TCM syndrome-based hypothesis for overcoming primary anti-PD-1 resistance in gastric cancer"],"prefix":"10.1136","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-4598-4327","authenticated-orcid":false,"given":"Yinghou","family":"Wang","sequence":"first","affiliation":[{"name":"Department of General Surgery, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6420-0244","authenticated-orcid":false,"given":"Guozheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1541-9714","authenticated-orcid":false,"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Liaoning University of Traditional Chinese Medicine Affiliated Hospital, Shenyang, Liaoning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9776-6162","authenticated-orcid":false,"given":"Lijie","family":"Zhou","sequence":"additional","affiliation":[{"name":"Liaoning University of Traditional Chinese Medicine Affiliated Hospital, Shenyang, Liaoning, China"},{"name":"Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5706-2583","authenticated-orcid":false,"given":"Yanyan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4932-5547","authenticated-orcid":false,"given":"Ye","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1897-3815","authenticated-orcid":false,"given":"Jingdong","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Liaoning University of Traditional Chinese Medicine Affiliated Hospital, Shenyang, Liaoning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6414-6493","authenticated-orcid":false,"given":"Yajie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"2026080405151501000_14.8.e015810.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)31288-5"},{"key":"2026080405151501000_14.8.e015810.2","unstructured":"Chinese Association of Integrative Medicine . Expert consensus for diagnosis and treatment of gastric cancer with integrated traditional Chinese and western medicine (T\/CAIM 016-2021). 2021."},{"key":"2026080405151501000_14.8.e015810.3","doi-asserted-by":"crossref","DOI":"10.3389\/fnut.2025.1594120","article-title":"cGAS-STING pathway as a promising target for digestive diseases: insights from natural plant products","volume":"12","author":"Long","year":"2025","journal-title":"Front Nutr"},{"key":"2026080405151501000_14.8.e015810.4","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2023-007104","article-title":"Outcomes and a prognostic classifier in patients with microsatellite instability-high metastatic gastric cancer receiving PD-1 blockade","volume":"11","author":"Randon","year":"2023","journal-title":"J Immunother Cancer"},{"key":"2026080405151501000_14.8.e015810.5","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-024-71974-3","article-title":"High levels of tumor cell-intrinsic STING signaling are associated with increased infiltration of CD8+ T cells in dMMR\/MSI-H gastric cancer","volume":"14","author":"Kanoda","year":"2024","journal-title":"Sci Rep"},{"key":"2026080405151501000_14.8.e015810.6","doi-asserted-by":"crossref","first-page":"2281","DOI":"10.1007\/s12094-024-03726-8","article-title":"Cancer cell-extrinsic STING shapes immune-active microenvironment and predicts clinical outcome in gastric cancer","volume":"27","author":"Wei","year":"2025","journal-title":"Clin Transl Oncol"},{"key":"2026080405151501000_14.8.e015810.7","doi-asserted-by":"crossref","first-page":"119035","DOI":"10.1016\/j.jep.2024.119035","article-title":"Evaluation of efficacy, safety and underlying mechanism on Traditional Chinese medicine as synergistic agents for cancer immunotherapy: A preclinical systematic review and meta-analysis","volume":"338","author":"Li","year":"2025","journal-title":"J Ethnopharmacol"},{"key":"2026080405151501000_14.8.e015810.8","doi-asserted-by":"crossref","first-page":"173","DOI":"10.7314\/APJCP.2013.14.1.173","article-title":"Tanshinone IIA reverses the malignant phenotype of SGC7901 gastric cancer cells","volume":"14","author":"Xu","year":"2013","journal-title":"Asian Pac J Cancer Prev"}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2026-015810","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T12:15:27Z","timestamp":1785845727000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2026-015810"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":8,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8,4]]},"published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1136\/jitc-2026-015810"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2026-015810","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]}}}