Personalized Neoantigen Vaccine plus Regorafenib Increases Rgs2⁺CD8⁺ T Cells Infiltration and Reprograms the Tumor Microenvironment in Microsatellite Stable Colorectal Cancer Liver Metastases.

ABSTRACT: Microsatellite stable colorectal cancer liver metastases (MSS-CRLM) resist immune checkpoint inhibitors due to their immunosuppressive tumor microenvironment (TME) and low mutation burden (TMB). A personalized neoantigen vaccine, Neo-CRCVAS, using whole-exome and RNA sequencing of murine MSS-CRC cells, comprising 7 immunogenic neoantigen peptides with Poly(I:C) is developed and combined with regorafenib as a novel therapy (RegoNeo). In MSS-CRLM mouse models, RegoNeo significantly enhanced tumor regression and survival while establishing durable immune memory. Single-cell RNA and TCR sequencing revealed that RegoNeo expanded a distinct Rgs2⁺CD8⁺ T cell population with strong cytotoxic activity and TCR clonal expansion. These Rgs2⁺CD8⁺ T cells, enriched for neoantigen-specific T cells, demon

SUBMITTER: Chen H 

PROVIDER: S-EPMC12462951 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature