2. Academic Validation
  3. Leveraging intratumoral probiotics for pancreatic cancer immunotherapy via xenophagy

Leveraging intratumoral probiotics for pancreatic cancer immunotherapy via xenophagy

  • Cell Host Microbe. 2026 Apr 8;34(4):657-671.e7. doi: 10.1016/j.chom.2026.02.010.
Baoyi Li 1,  Guangnian Liu 1,  Yu Zhu 1,  Lin Chen 2,  Nianhua Zhang 2,  Xiaojuan Zhu 3,  Yixin Sun 1,  Xinxin Liu 1,  Weikang Liu 4,  Yongsu Ma 4,  Xiaodong Tian 4,  Yinmo Yang 5,  Motao Zhu 6
Affiliations

Affiliations

  • 1 Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, Beijing 100034, China; CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China.
  • 2 CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China.
  • 3 Department of Pathology, Peking University First Hospital, Beijing 100034, China.
  • 4 Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, Beijing 100034, China.
  • 5 Department of Hepatobiliary and Pancreatic Surgery, Peking University First Hospital, Beijing 100034, China. Electronic address: [email protected].
  • 6 CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: [email protected].
PMID: 41794037 DOI: 10.1016/j.chom.2026.02.010
Abstract

Although pancreatic ductal adenocarcinoma (PDAC) tumors harbor unique intracellular bacteria, therapeutic strategies to harness them and overcome immunotherapy resistance remain elusive. Through 16S rDNA Sequencing of PDAC tumors from 40 patients and screening of probiotic strains, we identified Bifidobacterium longum (B. longum) as capable of colonizing tumors and invading PDAC cells. In a murine orthotopic tumor model, B. longum's anti-tumor effects are exclusively driven by rapamycin-induced xenophagy. This xenophagy-mediated probiotic therapy, termed XenoPro, significantly suppresses tumor growth by presenting B. longum-derived neoantigens and eliciting robust CD4+ T cell activation and tumor-specific cytotoxicity. From 40 predicted neoantigens, a vaccine containing the top 12 immunogenic neoantigens showed potent anti-tumor effects and prolonged survival in murine models of PDAC, colorectal Cancer, and melanoma. XenoPro, administered orally or intravenously, enhances immune cell infiltration and improves the efficacy of immune checkpoint inhibitors, offering a promising strategy for PDAC immunotherapy.

Keywords

Bifidobacterium longum; ICIs; PDAC; immune checkpoint inhibitors; pancreatic ductal adenocarcinoma; probiotic-mediated immunotherapy; rapamycin; xenophagy.

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