{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:49:14Z","timestamp":1785408554787,"version":"3.56.0"},"posted":{"date-parts":[[2026,4,17]]},"group-title":"Immunology","reference-count":41,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R01 CA269685"],"award-info":[{"award-number":["R01 CA269685"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"United States Department of Defense","doi-asserted-by":"crossref","award":["CA210457"],"award-info":[{"award-number":["CA210457"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000005","name":"United States Department of Defense","doi-asserted-by":"crossref","award":["CA230323"],"award-info":[{"award-number":["CA230323"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100031445","name":"NJCCR","doi-asserted-by":"crossref","award":["COCR26RBG006"],"award-info":[{"award-number":["COCR26RBG006"]}],"id":[{"id":"10.13039\/100031445","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Peritoneal metastases (PM) are the leading cause of cancer-related death in gastric cancer (GC) patients with survival typically &lt; 9 months. Here, we demonstrate that TIM3 and its ligands are increased along the GC continuum and associated with poor survival. Integrated omics analyses and functional studies revealed highly enriched TIM3 in CD163\n                  <jats:sup>+<\/jats:sup>\n                  tumor associated M2 immunosuppressive macrophages significantly promote tumor cell invasion and tumor growth\n                  <jats:italic>in vivo,<\/jats:italic>\n                  while TIM3 depletion in macrophages reduced tumor cell malignant attributes and increased T cell immunity from PBMCs or CD45+ immune cells of malignant ascites in co-culture system. By cytokine and kinase arrays, we discovered that depletion of TIM3 in macrophages reduced the production of notable secretome of cytokines\/chemokines from M2 macrophages; and the protumor function of TIM3\n                  <jats:sup>+<\/jats:sup>\n                  macrophages rely on the p90RSK1\/2\/CCL20 axis. Finally, we reveal that TIM3 blockage or genetic KO had superior antitumor activity in combination with anti-PD1 immunotherapy and mitomycin C (MMC) chemotherapy. Together, this study uncovers an important role for TIM3 in tumor associated M2 macrophages and underscores the potential of TIM3 blockage in GC patients with PM.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Statement of significance<\/jats:title>\n                  <jats:p>In this study, we show TIM3 increases along GC continuum, and highly enriched on tumor associated M2 macrophages that fuel tumor growth; and suppress T cell function via p90RSK1\/2\/CCL20 axis. TIM3 depletion restores T-cell immunity and curbs tumor growth. TIM3 blockade combined with anti-PD1 and mitomycin C provide a novel therapeutic strategy for GC patients with PM.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.04.15.716939","type":"posted-content","created":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T04:35:12Z","timestamp":1776486912000},"source":"Crossref","is-referenced-by-count":0,"title":["TIM3\n                  <sup>+<\/sup>\n                  Tumor Associated M2 Macrophages Impair Antitumor T Cell Immunity and Promote Gastric Cancer Progression and Peritoneal Metastasis"],"prefix":"10.64898","author":[{"given":"Xiaodan","family":"Yao","sequence":"first","affiliation":[{"name":"Coriell Institute for Medical Research, 403 Haddon Ave, Camden, NJ, 08103, USA"},{"name":"Camden Cancer Research Center, 403 Haddon Ave, Camden, NJ, 08103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibo","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dipti","family":"Athavale","sequence":"additional","affiliation":[{"name":"Coriell Institute for Medical Research, 403 Haddon Ave, Camden, NJ, 08103, USA"},{"name":"Camden Cancer Research Center, 403 Haddon Ave, Camden, NJ, 08103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Curt","family":"Balch","sequence":"additional","affiliation":[{"name":"Coriell Institute for Medical Research, 403 Haddon Ave, Camden, NJ, 08103, USA"},{"name":"Camden Cancer Research Center, 403 Haddon Ave, Camden, NJ, 08103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikel","family":"Ghelfi","sequence":"additional","affiliation":[{"name":"Coriell Institute for Medical Research, 403 Haddon Ave, Camden, NJ, 08103, USA"},{"name":"Camden Cancer Research Center, 403 Haddon Ave, Camden, NJ, 08103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Pompetti","sequence":"additional","affiliation":[{"name":"Coriell Institute for Medical Research, 403 Haddon Ave, Camden, NJ, 08103, USA"},{"name":"Camden Cancer Research Center, 403 Haddon Ave, Camden, NJ, 08103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Zhao","sequence":"additional","affiliation":[{"name":"Program in Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ailing","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiankang","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Gastrointestinal Medical 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