{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:24:23Z","timestamp":1787239463996,"version":"build-2736575974"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Cuiying Scientific and Technological Innovation Program of the Second Hospital and Clinical Medical School, Lanzhou University","award":["CY2024-MS-B07"],"award-info":[{"award-number":["CY2024-MS-B07"]}]},{"DOI":"10.13039\/501100004775","name":"Gansu Natural Science Foundation","doi-asserted-by":"publisher","award":["24JRRA379"],"award-info":[{"award-number":["24JRRA379"]}],"id":[{"id":"10.13039\/501100004775","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004775","name":"Natural Science Foundation of Gansu Province","doi-asserted-by":"publisher","award":["25JRZA153"],"award-info":[{"award-number":["25JRZA153"]}],"id":[{"id":"10.13039\/501100004775","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Cuiying Scientific Research, and Cultivation Program of the Second Hospital","award":["CYXZ2022-08"],"award-info":[{"award-number":["CYXZ2022-08"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the effect of gallic acid (GA) monomer on the cytotoxic function of tumour-infiltrating CD8+ T cells in gastric cancer and explore the underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Tumour-infiltrating CD8+ T cells were isolated from tumour tissues of patients with gastric adenocarcinoma using fluorescence-activated cell sorting. The purified CD8+ T cells were then co-incubated with GA at five different concentrations (0, 1, 2, 4, and 8\u00a0\u03bcM) for two incubation periods (24 and 48\u00a0h). Subsequently, the cytotoxic activity of tumour-infiltrating CD8+ T cells against gastric cancer cells was assessed using high-content live-cell tracking and cell counting assays. The apoptosis rates of gastric cancer cells were measured, and the expression of apoptosis-related factors caspase-3(p17), Bax, and Bcl-2 was analysed at both the transcriptional and protein levels. Additionally, secretion of IL-2, IL-4, IL-6, IFN-\u03b3, TNF-\u03b1, and IL-17 by tumour-inflitrating CD8+ T cells was evaluated to elucidate the potential mechanisms of GA-mediated immunomodulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key findings<\/jats:title>\n                    <jats:p>GA significantly enhanced the tumour-killing capacity of tumour-infiltrating CD8+ T cells (cell viability: 51.64% in the intervention group vs. 100% in the control group at 48\u00a0h), leading to increased gastric cancer cell apoptosis (apoptotic rate: 38.81% in the intervention group vs. 15.19% in the control group). Western blot and qRT-PCR results showed that the apoptosis executor, caspase-3(p17), and apoptotic molecular switch, Bax, were increased, while the anti-apoptotic protein, Bcl-2, was decreased. The augmented cytotoxicity of tumour-infiltrating CD8+ T cells was associated with statistically significant elevated secretions of pro-inflammatory cytokines Interferon-\u03b3 (IFN-\u03b3) (3.97\u00a0pg\/ml in the intervention group vs. 3.12\u00a0pg\/ml in the control group), Tumor Necrosis Factor-\u03b1 (TNF-\u03b1) (4.45\u00a0pg\/ml in the intervention group vs. 3.88\u00a0pg\/ml in the control group), and Interleukin-2 (IL-2) (5.82\u00a0pg\/ml in the intervention group vs. 5.22\u00a0pg\/ml in the control group). In contrast, the expression of IL-17A (43.74\u00a0pg\/ml in the intervention group vs. 49.38\u00a0pg\/ml in the control group) and IL-6 (4.13\u00a0pg\/ml in the intervention group vs. 4.61\u00a0pg\/ml in the control group) showed statistically significant decreases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>GA restored the impaired cytotoxic function of tumour-infiltrating CD8+ T cells in gastric cancer. These findings position GA as a potential novel immunomodulatory agent for improving anti-tumour immunity in gastric cancer treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jpp\/rgaf087","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T11:41:19Z","timestamp":1756467679000},"source":"Crossref","is-referenced-by-count":3,"title":["Gallic acid potentiates the tumour-killing function of CD8+ T cells in gastric cancer"],"prefix":"10.1093","volume":"78","author":[{"given":"Si","family":"Chen","sequence":"first","affiliation":[{"name":"Laboratory Medicine Center, The Second Hospital & Clinical Medical School, Lanzhou University , Lanzhou 730030, Gansu ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"HaiBin","family":"Wang","sequence":"additional","affiliation":[{"name":"CuiYing Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University , Lanzhou 730030, Gansu ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meixu","family":"Lei","sequence":"additional","affiliation":[{"name":"CuiYing Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University , Lanzhou 730030, Gansu ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumin","family":"Li","sequence":"additional","affiliation":[{"name":"Gansu Province Key Laboratory of Environmental Oncology, The Second Hospital & Clinical Medical School, Lanzhou University , Lanzhou 730030, Gansu ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Wang","sequence":"additional","affiliation":[{"name":"CuiYing Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University , Lanzhou 730030, Gansu ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hengxin","family":"Wang","sequence":"additional","affiliation":[{"name":"CuiYing Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University , Lanzhou 730030, Gansu ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Shen","sequence":"additional","affiliation":[{"name":"CuiYing Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University , Lanzhou 730030, Gansu ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejie","family":"Su","sequence":"additional","affiliation":[{"name":"CuiYing Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University , Lanzhou 730030, Gansu ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2074-443X","authenticated-orcid":false,"given":"Yali","family":"Zhou","sequence":"additional","affiliation":[{"name":"CuiYing Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University , Lanzhou 730030, Gansu ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,9,15]]},"reference":[{"key":"2026012010265893300_ref1","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1016\/S0140-6736(17)33326-3","article-title":"Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37513025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries","volume":"391","author":"Allemani","year":"2018","journal-title":"Lancet."},{"key":"2026012010265893300_ref2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.12968\/hmed.2024.0759","article-title":"Advances in immunotherapy and targeted therapy for gastric cancer: a comprehensive review","volume":"86","author":"Yuan","year":"2025","journal-title":"Br J Hosp Med (Lond)"},{"key":"2026012010265893300_ref3","doi-asserted-by":"publisher","first-page":"4296","DOI":"10.1038\/s41467-024-48307-z","article-title":"Targeting SOX13 inhibits assembly of respiratory chain supercomplexes to overcome ferroptosis resistance in gastric cancer","volume":"15","author":"Yang","year":"2024","journal-title":"Nat Commun"},{"key":"2026012010265893300_ref4","doi-asserted-by":"publisher","first-page":"e14489","DOI":"10.1111\/cns.14489","article-title":"A TGF-\u03b2 signaling-related lncRNA signature for prediction of glioma prognosis, immune microenvironment, and immunotherapy response","volume":"30","author":"Duan","year":"2024","journal-title":"CNS Neurosci Ther"},{"key":"2026012010265893300_ref5","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.jss.2023.03.042","article-title":"CD69 on tumor-infiltrating cells correlates with neuroblastoma suppression by simultaneous PD-1 and PD-L1 blockade","volume":"289","author":"Inoue","year":"2023","journal-title":"J Surg Res"},{"key":"2026012010265893300_ref6","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.4143\/crt.2024.317","article-title":"Effector function characteristics of exhausted CD8+ T-cell in microsatellite stable and unstable gastric cancer","volume":"56","author":"Han","year":"2024","journal-title":"Cancer Res Treat"},{"key":"2026012010265893300_ref7","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1007\/s11655-021-3345-2","article-title":"Gallic acid: a potential anti-cancer agent","volume":"28","author":"Jiang","year":"2022","journal-title":"Chin J Integr Med"},{"key":"2026012010265893300_ref8","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1007\/s12032-023-02178-4","article-title":"How gallic acid regulates molecular signaling: role in cancer drug resistance","volume":"40","author":"Hassani","year":"2023","journal-title":"Med Oncol"},{"key":"2026012010265893300_ref9","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1093\/toxres\/tfad024","article-title":"Celastrol inhibits gastric cancer cell proliferation, migration, and invasion via the FOXA1\/CLDN4 axis","volume":"12","author":"Peng","year":"2023","journal-title":"Toxicol Res (Camb)"},{"key":"2026012010265893300_ref10","doi-asserted-by":"crossref","first-page":"37","DOI":"10.3390\/ph16010037","article-title":"Afatinib reverses EMT via inhibiting CD44-Stat3 axis to promote radiosensitivity in nasopharyngeal carcinoma","volume":"16","author":"Huang","year":"2023","journal-title":"Pharmaceuticals"},{"key":"2026012010265893300_ref11","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21099-2","article-title":"Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy","volume":"12","author":"Riyao","year":"2021","journal-title":"Nat Commun"},{"key":"2026012010265893300_ref12","doi-asserted-by":"publisher","first-page":"107499","DOI":"10.1016\/j.phrs.2024.107499","article-title":"ARID1A is a coactivator of STAT5 that contributes to CD8+ T cell dysfunction and anti-PD-1 resistance in gastric cancer","volume":"210","author":"Fangqi","year":"2024","journal-title":"Pharmacol Res"},{"key":"2026012010265893300_ref13","doi-asserted-by":"publisher","first-page":"1432869","DOI":"10.3389\/fonc.2024.1432869","article-title":"Evaluation of a three-gene methylation model for correlating lymph node metastasis in postoperative early gastric cancer adjacent samples","volume":"14","author":"Chen","year":"2024","journal-title":"Front Oncol"},{"key":"2026012010265893300_ref14","doi-asserted-by":"publisher","first-page":"107596","DOI":"10.1016\/j.phrs.2025.107596","article-title":"Noncoding RNAs in sepsis-associated acute liver injury: roles, mechanisms, and therapeutic applications","volume":"212","author":"Wang","year":"2025","journal-title":"Pharmacol Res"},{"key":"2026012010265893300_ref15","doi-asserted-by":"publisher","first-page":"111028","DOI":"10.1016\/j.jtbi.2022.111028","article-title":"A mathematical model to study the impact of intra-tumour heterogeneity on anti-tumour CD8+ T cell immune response","volume":"538","author":"Leschiera","year":"2022","journal-title":"J Theor Biol"},{"key":"2026012010265893300_ref16","doi-asserted-by":"publisher","first-page":"e2202914","DOI":"10.1002\/advs.202202914","article-title":"Pyroptosis remodeling tumor microenvironment to enhance pancreatic cancer immunotherapy driven by membrane anchoring photosensitizer","volume":"9","author":"Wang","year":"2022","journal-title":"Adv Sci (Weinh)"},{"key":"2026012010265893300_ref17","doi-asserted-by":"crossref","first-page":"2408","DOI":"10.24976\/Discov.Med.202436191.222","article-title":"KDM4C and GFPT1: potential therapeutic targets for gastric cancer","volume":"36","author":"Li","year":"2024","journal-title":"Discov Med"},{"key":"2026012010265893300_ref18","doi-asserted-by":"publisher","first-page":"144444","DOI":"10.1016\/j.ijbiomac.2025.144444","article-title":"Tumor-targeting and redox-responsive photo-cross-linked nanogel derived from multifunctional hyaluronic acid-lipoic acid conjugates for enhanced in vivo protein delivery","volume":"314","author":"Sun","year":"2025","journal-title":"Int J Biol Macromol"},{"key":"2026012010265893300_ref19","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1002\/ptr.8082","article-title":"Phytochemicals in regulating PD-1\/PD-L1 and immune checkpoint blockade therapy","volume":"38","author":"Zhang","year":"2024","journal-title":"Phytother Res"},{"key":"2026012010265893300_ref20","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.24976\/Discov.Med.202436189.187","article-title":"The evaluation of gastric cancer lymphovascular invasion using CT volume perfusion","volume":"36","author":"Li","year":"2024","journal-title":"Discov Med"},{"key":"2026012010265893300_ref21","doi-asserted-by":"publisher","first-page":"e22638","DOI":"10.1002\/jbt.22638","article-title":"Gallic acid potentiates the apoptotic effect of paclitaxel and carboplatin via overexpression of Bax and P53 on the MCF-7 human breast cancer cell line","volume":"35","author":"Aborehab","year":"2021","journal-title":"J Biochem Mol Toxicol"},{"key":"2026012010265893300_ref22","doi-asserted-by":"publisher","first-page":"1860482","DOI":"10.1080\/2162402X.2020.1860482","article-title":"T cells expanded from renal cell carcinoma display tumor-specific CD137 expression but lack significant IFN-\u03b3, TNF-\u03b1 or IL-2 production","volume":"10","author":"Asten","year":"2021","journal-title":"Oncoimmunology."},{"key":"2026012010265893300_ref23","doi-asserted-by":"publisher","first-page":"e2308711","DOI":"10.1002\/advs.202308711","article-title":"VEGF-FGF signaling activates quiescent CD63+ liver stem cells to proliferate and differentiate","volume":"11","author":"Chen","year":"2024","journal-title":"Adv Sci"},{"key":"2026012010265893300_ref24","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1186\/s12885-020-07181-w","article-title":"Differential associations of proinflammatory and anti-inflammatory cytokines with depression severity from noncancer status to breast cancer course and subsequent chemotherapy","volume":"20","author":"Tzang","year":"2020","journal-title":"BMC Cancer"},{"key":"2026012010265893300_ref25","doi-asserted-by":"publisher","first-page":"W520","DOI":"10.1093\/nar\/gkad408","article-title":"SEanalysis 2.0: a comprehensive super-enhancer regulatory network analysis tool for human and mouse","volume":"51","author":"Qian","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"2026012010265893300_ref26","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1038\/s43018-024-00775-4","article-title":"Tumor-associated macrophages restrict CD8+ T cell function through collagen deposition and metabolic reprogramming of the breast cancer microenvironment","volume":"5","author":"Tharp","year":"2024","journal-title":"Nat Cancer"},{"key":"2026012010265893300_ref27","doi-asserted-by":"publisher","first-page":"e000692","DOI":"10.1136\/jitc-2020-000692","article-title":"IFN-\u03b3 treatment protocol for MHC-Ilo\/PD-L1+ pancreatic tumor cells selectively restores their TAP-mediated presentation competence and CD8 T-cell priming potential","volume":"8","author":"Stifter","year":"2020","journal-title":"J Immunother Cancer"},{"key":"2026012010265893300_ref28","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/j.trecan.2024.03.008","article-title":"Gastric cancer immunosuppressive microenvironment heterogeneity: implications for therapy development","volume":"10","author":"Yasuda","year":"2024","journal-title":"Trends Cancer"},{"key":"2026012010265893300_ref29","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1016\/j.semcancer.2020.12.001","article-title":"Pivotal role of PD-1\/PD-L1 immune checkpoints in immune escape and cancer progression: their interplay with platelets and FOXP3+Tregs related molecules, clinical implications and combinational potential with phytochemicals","volume":"86","author":"Lee","year":"2022","journal-title":"Semin Cancer Biol"}],"container-title":["Journal of Pharmacy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/78\/1\/rgaf087\/64273690\/rgaf087.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/78\/1\/rgaf087\/64273690\/rgaf087.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T15:27:05Z","timestamp":1768922825000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpp\/article\/doi\/10.1093\/jpp\/rgaf087\/8254310"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,15]]},"references-count":29,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1,16]]}},"URL":"https:\/\/doi.org\/10.1093\/jpp\/rgaf087","relation":{},"ISSN":["0022-3573","2042-7158"],"issn-type":[{"value":"0022-3573","type":"print"},{"value":"2042-7158","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,1]]},"published":{"date-parts":[[2025,9,15]]},"article-number":"rgaf087"}}