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Information about the disease is limited. Here we employed single\u2010cell RNA sequencing to investigate peripheral blood mononuclear cells (PBMCs), aiming to unravel the immune response of patients toward HAGC. PBMCs from seven HAGC patients, six normal advanced gastric cancer (NAGC) patients, and five healthy individuals were analysed by single\u2010cell RNA sequencing. The expression of genes of interest was validated by bulk RNA\u2010sequencing and ELISA. We found a massive expansion of neutrophils in PBMCs of HAGC. These neutrophils are activated, but immature. Besides, mononuclear phagocytes exhibited an M2\u2010like signature and T cells were suppressed and reduced in number. Analysis of cell\u2010cell crosstalk revealed that several signalling pathways involved in neutrophil to T\u2010cell suppression including APP\u2010CD74, MIF\u2010(CD74+CXCR2), and MIF\u2010(CD74+CD44) pathways were increased in HAGC. NETosis\u2010associated genes S100A8 and S100A9 as well as VEGF, PDGF, FGF, and NOTCH signalling that contribute to DIC development were upregulated in HAGC too. This study reveals significant changes in the distribution and interactions of the PBMC subsets and provides valuable insight into the immune response in patients with HAGC. S100A8 and S100A9 are highly expressed in HAGC neutrophils, suggesting their potential to be used as novel diagnostic and therapeutic targets for HAGC.<\/jats:p>","DOI":"10.1111\/cpr.13591","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T01:59:10Z","timestamp":1707271150000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Single\u2010cell RNA sequencing reveals immune cell dysfunction in the peripheral blood of patients with highly aggressive gastric cancer"],"prefix":"10.1111","volume":"57","author":[{"given":"Rui","family":"Ma","sequence":"first","affiliation":[{"name":"Guangdong Institute of Gastroenterology  Guangzhou China"},{"name":"Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease The Sixth Affiliated Hospital, Sun Yat\u2010sen University  Guangzhou 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Proliferation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cpr.13591","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T02:59:39Z","timestamp":1714359579000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cpr.13591"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,6]]},"references-count":46,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1111\/cpr.13591"],"URL":"https:\/\/doi.org\/10.1111\/cpr.13591","archive":["Portico"],"relation":{},"ISSN":["0960-7722","1365-2184"],"issn-type":[{"value":"0960-7722","type":"print"},{"value":"1365-2184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,6]]},"assertion":[{"value":"2023-10-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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