2. Academic Validation
  3. In situ DC-primed vaccine combined with CD137 agonist elicits long-lasting antitumor immunity through cDC1-mediated tumor antigen-specific CD8+ T cell responses

In situ DC-primed vaccine combined with CD137 agonist elicits long-lasting antitumor immunity through cDC1-mediated tumor antigen-specific CD8+ T cell responses

  • J Immunother Cancer. 2025 Dec 12;13(12):e011665. doi: 10.1136/jitc-2025-011665.
Mengjiao Wang # 1 2 3,  Li Qiu # 4 5,  Cheng Tang # 5,  Danqing Huang # 6,  Qiaocong Zheng 2,  Zunyi Li 7,  Zhenhui Zhang 8,  Shupei Wei 5,  Lanfang Chen 1 2,  Hongxin Huang 5,  Jun Liu 8,  Junfeng Zhou 5,  Tao Lu 5,  Guanxin Liu 1 2,  Yingjie Nie 9,  Qibin Leng 10,  Tao Chen 11
Affiliations

Affiliations

  • 1 Department of Pulmonary and Critical Care Medicine, Zigong First People's Hospital, Zigong, Sichuan, People's Republic of China.
  • 2 State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.
  • 3 Institute of Modern Biology, Nanjing University, Nanjing, Jiangsu, People's Republic of China.
  • 4 Department of Thoracic Surgery, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University National Clinical Research Center for Respiratory Diseases, Guangzhou, Guangdong, People's Republic of China [email protected] [email protected] [email protected] [email protected].
  • 5 State Key Laboratory of Respiratory Disease, Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.
  • 6 Guangzhou Key Laboratory for Research and Development of Nano-Biomedical Technology for Diagnosis and Therapy &Guangdong Provincial Education Department Key Laboratory of Nano-Immunoregulation Tumor Microenvironment, Department of Oncology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.
  • 7 Department of Basic Medicine, Army Medical University, Chongqing, People's Republic of China.
  • 8 Department of Thoracic Surgery, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University National Clinical Research Center for Respiratory Diseases, Guangzhou, Guangdong, People's Republic of China.
  • 9 Shenzhen Key Laboratory for Cancer Metastasis and Personalized Therapy, Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, People's Republic of China [email protected] [email protected] [email protected] [email protected].
  • 10 State Key Laboratory of Respiratory Disease, Guangzhou Institute of Cancer Research, The Affiliated Cancer Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China [email protected] [email protected] [email protected] [email protected].
  • 11 State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China [email protected] [email protected] [email protected] [email protected].
  • # Contributed equally.
PMID: 41386973 DOI: 10.1136/jitc-2025-011665
Abstract

Background: Intratumoral vaccines offer a promising avenue in Cancer Immunotherapy by harnessing the tumor microenvironment to stimulate immune responses. However, challenges persist in maximizing their effectiveness and addressing immune suppression within tumors.

Methods: Conventional in situ vaccine (CisVac) and α-CD137 antibody were administered in implanted mouse models of lung and colon Cancer to evaluate therapeutic efficacy. The initiation mechanism of CD8+ T cells was determined using antibody blockade and transgenic mouse models. Single-cell RNA Sequencing was used to further characterize the activation mechanism of T cells.

Results: Our findings indicate that this synergistic approach markedly inhibits tumor growth while eliciting a robust antitumor immune response, characterized by heightened activation and cytotoxic differentiation of CD8+ T cells, as well as the polarization of conventional dendritic cells (cDC1). Mechanistically, it promotes the cDC1-dependent proportion and cytokine production of tumor antigen-specific CD8+ T cells, mobilizes and establishes enduring systemic immune memory. Our single-cell transcriptome analyses revealed that the therapy facilitates a functional remodeling of regulatory T cells (Tregs) with upregulated inflammatory genes, potentially attenuating immune suppression. Cell-cell communication analyses highlighted interactions between CD4+ Th1-like/Th17 cells and monocytes/DCs through the CD40L-CD40 pathway, indicating potential intercellular regulatory mechanisms.

Conclusions: Our results highlight the transformative potential of the CisVac/α-CD137 combination in Cancer Immunotherapy, paving the way for further exploration of its clinical utility and long-term efficacy.

Keywords

Combination therapy; Dendritic; Solid tumor; Toll-like receptor - TLR; Vaccine.

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