TIM3 <sup>+</sup> Tumor Associated M2 Macrophages Impair Antitumor T Cell Immunity and Promote Gastric Cancer Progression and Peritoneal Metastasis
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. Statement of significance: 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.
Authors
- Young Ki Hong (ORCID: https://orcid.org/0000-0001-6634-1367)
- L L W Wang
- Yibo Fan (ORCID: https://orcid.org/0000-0001-7589-4158)
- Ailing W. Scott (ORCID: https://orcid.org/0009-0005-1473-1116)
- Jaffer A. Ajani (ORCID: https://orcid.org/0000-0001-9946-0629)
- Raghav Sundar (ORCID: https://orcid.org/0000-0001-9423-1368)
- Mikel D. Ghelfi (ORCID: https://orcid.org/0000-0002-8238-9560)
- Dipti Athavale (ORCID: https://orcid.org/0000-0003-0688-4970)
- Generosa Grana (ORCID: https://orcid.org/0000-0002-3528-9516)
- Jiankang Jin (ORCID: https://orcid.org/0000-0001-9864-9817)
- Joseph Zhao
- Curt Balch (ORCID: https://orcid.org/0000-0002-7878-156X)
- Francis J. Spitz (ORCID: https://orcid.org/0009-0003-0905-2683)
- Anthony Pompetti
- Junsong Zhao
- Jimmy Bok-Yan So
- Jamin Morrison
- Yan-ting Yann Zhang
- Shumei Song
- Xiaodan Yao (ORCID: https://orcid.org/0009-0004-7322-0036)
- Madeline Torres
- Patrick Tan
- Shilpa S Dhar
Institutions
- Rutgers, The State University of New Jersey (US)
- The University of Texas MD Anderson Cancer Center (US)
- Cooper University Hospital (US)
- Coriell Institute For Medical Research (US)
- Yale Cancer Center (US)
- Cooper Medical School of Rowan University (US)
- Duke-NUS Medical School (SG)
- Cancer Research Center (US)
- National University Hospital (SG)
- National University Health System (SG)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2026-04-17
- DOI
- https://doi.org/10.64898/2026.04.15.716939
- Primary Topic
- Cancer Mechanisms and Therapy
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- U.S. Department of Defense
- New Jersey Commission on Cancer Research