Abstract
Prophylactically-induced brain-resident memory CD8+ T cells provide durable protection against intracranial malignancy 2089
The Journal of immunology (1950), Vol.214(Supplement_1), vkaf283053
11/01/2025
DOI: 10.1093/jimmun/vkaf283.053
Abstract
Abstract Description
Primary and metastatic brain tumors are clinically refractory to immunotherapies that demonstrate efficacy in peripheral cancer settings. While many immunotherapies aim to enhance CD8+ T cell infiltration and functionality in fully established tumors, the utility of immunoprevention against brain cancer remains understudied. Numerically enriched and functionally potent tissue-resident memory (TRM) CD8+ T cells can be generated in healthy brain tissue following peripheral infection and vaccination. However, the ability of prophylactically-seeded, tumor-specific brain TRM to protect against intracranial malignancy remains unknown. Here, we developed models where mice were seeded with tumor-specific or bystander brain TRM via peripheral infection prior to brain tumor challenge. Tumor-specific, but not bystander, brain TRM durably protected mice against intracranial malignancy even in the absence of circulating memory T cells (TCIRCM). These brain TRM persisted long-term in tumor survivors and prevented mortality against a second antigen-matched intracranial challenge. Importantly, a translationally relevant mRNA vaccine encoding tumor-derived epitopes phenocopied peripheral infection-induced outcomes, generating functional brain TRM that intercepted tumor growth. Altogether, this work points to the prophylactic utility of brain TRM in tumor immunoprevention and supports the development of anti-cancer mRNA vaccines as a non-invasive approach to bolster brain immunity.
Funding Sources
NIH/NIAID R21AI178159 NIH/NIAID R21AI185067 NIH/NIAID T32AI007260 NIH/NIGMS T32GM139776 NIH/NIAID F32AI174382 University of Iowa Graduate College Post-Comprehensive Research Fellowship
Topic Categories
Neuroimmunology (NEUR)
Details
- Title: Subtitle
- Prophylactically-induced brain-resident memory CD8+ T cells provide durable protection against intracranial malignancy 2089
- Creators
- Madison R Mix - University of IowaCassie M Sievers - University of IowaMariah A HassertShravan Kumar KannanLecia Lynn EppingSunny C HuangRui HeCori E Fain - University of IowaLisa S Hancox - University of IowaSahaana A ArumugamAliasger K SalemVladimir P Badovinac - University of IowaJohn T Harty - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The Journal of immunology (1950), Vol.214(Supplement_1), vkaf283053
- DOI
- 10.1093/jimmun/vkaf283.053
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Publisher
- Oxford University Press; OXFORD
- Grant note
- NIH/NIAID: R21AI178159, R21AI185067, T32AI007260, F32AI174382 NIH/NIGMS: T32GM139776 University of Iowa Graduate College Post-Comprehensive Research Fellowship
NIH/NIAID R21AI178159 NIH/NIAID R21AI185067 NIH/NIAID T32AI007260 NIH/NIGMS T32GM139776 NIH/NIAID F32AI174382 University of Iowa Graduate College Post-Comprehensive Research Fellowship
- Alternative title
- IMMUNOLOGY2025™ Abstracts
- Language
- English
- Date published
- 11/01/2025
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Research Administration; Pathology; Pharmaceutical Sciences and Experimental Therapeutics; Radiation Oncology; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering
- Record Identifier
- 9985034937802771
Metrics
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