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Peer-reviewedCC BY-NC-ND 4.0Nature Communications

In situ reprogramming of glioma stem cells into dendritic cell-like cells for glioblastoma immunotherapy

  • Chunwei Tang
  • Weiyi Sun
  • Zhenmei Yang
  • Xiaotian Zhao
  • Jian Gao
  • Kun Han
  • Zichao Yao
  • Xianghui Dong
  • Miaoyan Liu
  • Jing Zhang
  • Zhaoyu Chen1
  • Xiao Yue
11 more authors
  • Zhipeng Fu
  • Yan Wang
  • Maosen Han
  • Ying Liu
  • Jinxin Gao
  • Yulin Zhang2
  • Xinyi Jiang
  • Chen Chen
  • Xin Wen
  • Kun Zhao
  • Jingyi Han
  1. 1Shandong University of Traditional Chinese Medicine, Jinan, China
  2. 2Department of Neurosurgery, Qilu Hospital and Institute of Brain and Brain-Inspired Science, Cheeloo College of Medicine, Shandong University, Jinan, China
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Abstract

Immunotherapy has revolutionized the treatment landscape for many cancers, but fails to improve the outcomes of glioblastoma multiforme (GBM), in which low tumor antigen presentation restricts the recognition and eradication of cancerous cells by immunocytes. We here report an approach to in situ reprogramming hypoimmunogenic glioblastoma stem cells (GSCs) into type 1 conventional dendritic cell (cDC1)-like cells for presenting endogenous tumor antigens and priming sustained tumoricidal T-cell responses. Specifically, our cavity-injectable nucleobase-derived lipid nanoparticle (LNP)-hydrogel superstructure efficiently delivers transcription factors (PU.1, IRF8, BATF3) and the costimulatory molecule (TNFSF9) into GSCs to induce cDC1-like reprogramming. These cDC1-like cells potentiate GBM immunogenicity, elicit robust adaptive immunity and long-term antitumor memory, thereby inhibiting tumor growth and preventing postoperative GBM relapse in mice. Collectively, this work establishes in situ tumor cell reprogramming into licensed cDC1-like cells as a therapeutic paradigm for converting immunologically “cold” tumors into a self-vaccinating immune niche with broad translational potential for hypoimmunogenic malignancy treatment.

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Cite

BibTeXRIS
BibTeX
@article{tang2026situ,
  title = {{In situ reprogramming of glioma stem cells into dendritic cell-like cells for glioblastoma immunotherapy}},
  author = {Chunwei Tang and Weiyi Sun and Zhenmei Yang and Xiaotian Zhao and Jian Gao and Kun Han and Zichao Yao and Xianghui Dong and Miaoyan Liu and Jing Zhang and Zhaoyu Chen and Xiao Yue and Zhipeng Fu and Yan Wang and Maosen Han and Ying Liu and Jinxin Gao and Yulin Zhang and Xinyi Jiang and Chen Chen and Xin Wen and Kun Zhao and Jingyi Han},
  journal = {Nature Communications},
  year = {2026},
  month = sep,
  doi = {10.1038/s41467-026-78070-2},
  url = {https://doi.org/10.1038/s41467-026-78070-2},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - In situ reprogramming of glioma stem cells into dendritic cell-like cells for glioblastoma immunotherapy
AU  - Chunwei Tang
AU  - Weiyi Sun
AU  - Zhenmei Yang
AU  - Xiaotian Zhao
AU  - Jian Gao
AU  - Kun Han
AU  - Zichao Yao
AU  - Xianghui Dong
AU  - Miaoyan Liu
AU  - Jing Zhang
AU  - Zhaoyu Chen
AU  - Xiao Yue
AU  - Zhipeng Fu
AU  - Yan Wang
AU  - Maosen Han
AU  - Ying Liu
AU  - Jinxin Gao
AU  - Yulin Zhang
AU  - Xinyi Jiang
AU  - Chen Chen
AU  - Xin Wen
AU  - Kun Zhao
AU  - Jingyi Han
PY  - 2026
DA  - 2026/09/28
JO  - Nature Communications
DO  - 10.1038/s41467-026-78070-2
UR  - https://doi.org/10.1038/s41467-026-78070-2
AB  - Immunotherapy has revolutionized the treatment landscape for many cancers, but fails to improve the outcomes of glioblastoma multiforme (GBM), in which low tumor antigen presentation restricts the recognition and eradication of cancerous cells by immunocytes. We here report an approach to in situ reprogramming hypoimmunogenic glioblastoma stem cells (GSCs) into type 1 conventional dendritic cell (cDC1)-like cells for presenting endogenous tumor antigens and priming sustained tumoricidal T-cell responses. Specifically, our cavity-injectable nucleobase-derived lipid nanoparticle (LNP)-hydrogel superstructure efficiently delivers transcription factors (PU.1, IRF8, BATF3) and the costimulatory molecule (TNFSF9) into GSCs to induce cDC1-like reprogramming. These cDC1-like cells potentiate GBM immunogenicity, elicit robust adaptive immunity and long-term antitumor memory, thereby inhibiting tumor growth and preventing postoperative GBM relapse in mice. Collectively, this work establishes in situ tumor cell reprogramming into licensed cDC1-like cells as a therapeutic paradigm for converting immunologically “cold” tumors into a self-vaccinating immune niche with broad translational potential for hypoimmunogenic malignancy treatment.
SN  - 2041-1723
ER  -