Enhancing gastric cancer immunotherapy: Insights from multi-omics analysis and innovations in photodynamic-chemotherapy nanoplatforms

  • Cell Rep Med. 2026 Mar 17;7(3):102635. doi: 10.1016/j.xcrm.2026.102635.
Qing-Zhu Qiu  1 ,  You-Xin Gao  1 ,  Yu-Xuan Zhao  1 ,  Deng-Hui Fan  1 ,  Xin-Peng Yang  1 ,  Tong-Xing Lin  2 ,  Chen-Yang Jiang  1 ,  Ze-Ning Huang  1 ,  Qiao-Ling Zheng  3 ,  Zhi-Hong Huang  4 ,  Yi Li  1 ,  Chao-Hui Zheng  1 ,  Ping Li  1 ,  Jian-Wei Xie  1 ,  Jia-Bin Wang  1 ,  Sachiyo Nomura  5 ,  Qi Chen  6 ,  Qi-Yue Chen  7 ,  Chang-Ming Huang  8
Affiliations
  • 1. Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Ministry of Education), Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China.
  • 2. Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of Emergency Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
  • 3. Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, China.
  • 4. Public Technology Service Center, Fujian Medical University, Fuzhou, China.
  • 5. Department of Clinical Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
  • 6. Interdisciplinary Institute for Medical Engineering, Fuzhou University, Fuzhou, China. Electronic address: [email protected].
  • 7. Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Ministry of Education), Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China. Electronic address: [email protected].
  • 8. Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China; Key Laboratory of Gastrointestinal Cancer (Ministry of Education), Fujian Medical University, Fuzhou, China; Fujian Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou, China. Electronic address: [email protected].
PMID: 41747719 DOI: 10.1016/j.xcrm.2026.102635
Abstract

Overcoming resistance to immune checkpoint blockade (ICB) therapy in gastric Cancer (GC) remains a major clinical challenge. Here, we apply multi-omics profiling, including single-cell RNA Sequencing and spatial transcriptomics, to GC tissues from patients receiving neoadjuvant ICB therapy to identify drivers of resistance. We identify tumor-intrinsic Yes-associated protein 1 (YAP1) as a key regulator of immunosuppressive cellular communities that contribute to ICB non-responsiveness. To mitigate the off-target toxicity of verteporfin, a YAP1 inhibitor, we develop macrophage-membrane-camouflaged hollow mesoporous silica nanoparticles (M@O-VNPs) co-loaded with verteporfin and oxaliplatin. This nanoplatform selectively inhibits YAP1, suppresses the CXCL5-CXCR2 axis, and reduces the activity of SPP1+ macrophages. By inducing immunogenic cell death, M@O-VNPs remodel the tumor microenvironment and enhance ICB efficacy while minimizing systemic toxicity. The therapeutic potential of this strategy is supported by synergistic antitumor effects of M@O-VNPs combined with anti-PD-1 therapy in genetically engineered and syngeneic GC models.

Keywords
gastric cancer; immunotherapy; multi-omics; nanoplatforms; tumor microenvironment.
Products
Inhibitors & Agonists
Other Products