Local delivery of interferon restores antigen presentation and sensitizes medulloblastoma to T cell killing

Medulloblastomas are considered immunologically cold and refractory to immunotherapy. One factor contributing to their low immunogenicity is impaired antigen presentation, which allows tumor cells to evade cytotoxic T cells. Using a syngeneic mouse model of medulloblastoma, we demonstrate that despite low expression of MHC class I on tumor cells, depletion of CD8 + T cells accelerates tumor growth, whereas adoptive transfer of tumor-reactive CD8 + T cells prolongs survival. These antitumor effects rely on T cell–derived interferon gamma (IFNγ), which induces MHC class I on tumor cells and facilitates tumor cell killing by T cells. Importantly, delivering IFNγ directly into tumors via convection-enhanced delivery enhances CD8 + T cell–mediated killing of tumor cells and significantly prolongs survival in tumor-bearing mice. These studies highlight the importance of T cells in controlling brain tumors and the value of IFNγ as an adjuvant for T cell–based immunotherapy.

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Publication Details

Journal
Proceedings of the National Academy of Sciences
Published
2026-09-14
DOI
https://doi.org/10.1073/pnas.2531269123
Primary Topic
Glioma Diagnosis and Treatment
Type
article
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article

Local delivery of interferon restores antigen presentation and sensitizes medulloblastoma to T cell killing

Yanxin Pei, Meher Beigi Masihi, Scott L. Pomeroy, Koei Chin et al.
Proceedings of the National Academy of Sciences
Glioma Diagnosis and Treatment
article

Local delivery of interferon restores antigen presentation and sensitizes medulloblastoma to T cell killing

Yanxin Pei, Meher Beigi Masihi, Scott L. Pomeroy, Koei Chin, Ernest Fraenkel, Veronika I. Pister, Theophilos Tzaridis, Lukas Chávez, Tanja Eisemann, Kendall R. Chambers, Robert J. Wechsler‐Reya, Alexander T. Wenzel, Jill P. Mesirov, Sajina GC, Aditi Dutta, Anindya Bagchi, Isaac Youm, Zhenhua Xu
article en

Abstract

Medulloblastomas are considered immunologically cold and refractory to immunotherapy. One factor contributing to their low immunogenicity is impaired antigen presentation, which allows tumor cells to evade cytotoxic T cells. Using a syngeneic mouse model of medulloblastoma, we demonstrate that despite low expression of MHC class I on tumor cells, depletion of CD8 + T cells accelerates tumor growth, whereas adoptive transfer of tumor-reactive CD8 + T cells prolongs survival. These antitumor effects rely on T cell–derived interferon gamma (IFNγ), which induces MHC class I on tumor cells and facilitates tumor cell killing by T cells. Importantly, delivering IFNγ directly into tumors via convection-enhanced delivery enhances CD8 + T cell–mediated killing of tumor cells and significantly prolongs survival in tumor-bearing mice. These studies highlight the importance of T cells in controlling brain tumors and the value of IFNγ as an adjuvant for T cell–based immunotherapy.

Proceedings of the National Academy of SciencesVol. 123(38)
Broad Institute (US), Boston Children's Hospital (US), Harvard University (US), Oregon Health & Science University (US), George Washington University (US), Discovery Institute (US), Columbia University Irving Medical Center (US), University of California San Diego (US), National Cancer Center (US), Massachusetts Institute of Technology (US)
Openalex Percentile: Top 11%
Glioma Diagnosis and Treatment
DOIOpen Access PDFOpenAlex
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