Work

Prophylactically-induced brain-resident memory CD8+ T cells provide durable protection against intracranial malignancy 2089

Year: 2025

Type: article

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)

Source: The Journal of Immunology

DOI: 10.1093/jimmun/vkaf283.053