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

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

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.

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