GSE124620
Virus-specific memory T cells populate tumors and can be repurposed for tumor immunotherapy
Improvements in cancer immunotherapy are needed. The immunosuppressive tumor microenvironment limits the success of current immunotherapies. The host retains memory T cells specific for previous infections throughout the entire body that are capable of executing potent and immediate immunostimulatory functions. Here we show that virus-specific memory T cells extend their surveillance to mouse and human tumors. Reactivating these antiviral T cells can arrest growth of checkpoint blockade-resistant and poorly immunogenic tumors in mice after injecting adjuvant-free non-replicating viral peptides into tumors. Peptide mimics a viral reinfection event to memory CD8+ T cells, triggering antigen presentation and cytotoxic pathways within the tumor, activating dendritic cells and natural killer cells, and recruiting the adaptive immune sytem. Viral peptide treatment of ex vivo human tumors recapitulates immune activation gene expression profiles in mice. Lastly, peptide therapy renders resistant mouse tumors susceptible to PD-L1 blockade. Thus, re-stimulating known antiviral immunity may provide a unique therapeutic approach for cancer immunotherapy. Overall design: For B16 mouse tumor studies, B16 tumors in OT-1 chimeras were treated with relevant or irrelevant viral peptide. 9 hours after peptide delivery, B16 tumors were harvested from 3 mice per group. RNA was isolated from tumor homogenate for sequencing. For Braf/Pten tumor studies, murine melanoma tumors in OT-1 chimeras were isolated, sliced into thin sections, and incubated with relevant or irrelevant peptide ex vivo. RNA was isolated from tumor culture homogenate for sequencing. For human tumor samples, tumors were sliced into thin sections, and incubated with relevant or irrelevant viral peptides ex vivo. RNA was isolated from tumor culture homogenate for sequencing.