Journal article
Peripheral vaccination-induced brain-resident memory CD8+ T cells durably protect mice against intracranial malignancy
The Journal of clinical investigation, Vol.136(8), e41983390
04/15/2026
DOI: 10.1172/JCI197812
PMID: 41983390
Abstract
Primary and metastatic brain tumors exhibit resistance to immunotherapies that demonstrate efficacy in peripheral cancer settings. While many immunotherapies aim to enhance CD8+ T cell infiltration and functionality in established tumors, identification of neoantigens support emerging immunopreventative tactics against brain cancer. Functionally potent tissue-resident memory CD8+ T cells (TRM) can be generated in the brain following peripheral infection or vaccination. However, the ability of brain TRM to prevent intracranial malignancy remains unknown. Here, mice were seeded with tumor-specific or bystander brain TRM via peripheral infection prior to depletion of circulating memory T cells (TCIRCM) and subsequent brain tumor challenge. Tumor-specific brain TRM durably protected mice against intracranial malignancy even in the absence TCIRCM. These brain TRM persisted in tumor-surviving mice and protected against a second antigen-matched challenge. Importantly, a translationally-relevant mRNA-lipid nanoparticle (LNP) vaccine phenocopied peripheral infection-induced outcomes, generating functional brain TRM that controlled tumor growth. Altogether, this work points to the utility of brain TRM in cancer immunoprevention, supporting the development of antitumor mRNA-LNP vaccines to bolster brain immunity.
Mix et al. demonstrate that the generation of anti-tumor brain-resident memory CD8+ T cells via peripheral vaccination can significantly attenuate adverse outcomes associated with brain malignancy.
Details
- Title: Subtitle
- Peripheral vaccination-induced brain-resident memory CD8+ T cells durably protect mice against intracranial malignancy
- Creators
- Madison R. Mix - Carver Bible CollegeCassie M. Sievers - Carver Bible CollegeMariah Hassert - Carver Bible CollegeShravan Kumar Kannan - University of IowaLecia L. Pewe - Carver Bible CollegeSunny C. Huang - University of IowaRui HeCori E. Fain - Carver Bible CollegeMohammad Heidarian - University of IowaLisa S. Hancox - Carver Bible CollegeSahaana A. Arumugam - Carver Bible CollegeTerry G. Beltz - University of IowaFang Jin - Mayo ClinicAaron J. Johnson - Mayo ClinicCalvin S. Carter - University of IowaNoah S. Butler - University of IowaAliasger K. Salem - University of IowaVladimir P. Badovinac - University of IowaJohn T. Harty - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.136(8), e41983390
- DOI
- 10.1172/JCI197812
- PMID
- 41983390
- NLM abbreviation
- J Clin Invest
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Publisher
- American Society for Clinical Investigation; ANN ARBOR
- Grant note
- 01 / HHMI Hanna H. Gray Fellow Program
- Language
- English
- Date published
- 04/15/2026
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Microbiology and Immunology; Research Administration; Pathology; Pharmaceutical Sciences and Experimental Therapeutics; Radiation Oncology; Craniofacial Anomalies Research Center; Neuroscience and Pharmacology; Dental Research; Chemical and Biochemical Engineering
- Record Identifier
- 9985153534002771
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