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Concurrent delivery of immune checkpoint blockade improves tumor microenvironment for vaccine-generated immunity

ABSTRACT: Neoantigen vaccines aiming to induce and amplify tumor-specific T cell responses have received promising anti-tumor effect in early clinical trials. However, the underlying mechanism regarding response or resistance to this treatment remains unclear. Here, we observed that neoantigen vaccine-generated T cells could synergize with immune checkpoint blockade (ICB) for effective tumor control. Specifically, we performed single-cell sequencing on over 100,000 T cells and uncovered that combined therapy induced a novel antigen-specific CD8 T cell population with active chemokine signaling (Cxcr3+/Ccl5+), lower co-inhibitory receptor expression (Lag3-/Havcr2-) and higher cytotoxicity (Fasl+/Gzma+). Furthermore, the generation of antigen specific T cells in the drain lymph node is required for combination treatment mediated therapeutic effect. Signature genes of this unique population is associated with T cell clonal frequency and better survival in human. Our study comprehensively profiled the dynamics of tumor infiltrated T cells during neoantigen vaccine and ICB treatments, and high-dimensionally identified neoantigen-reactive T cell signatures for future development of better therapeutic strategies.

ORGANISM(S): Mus musculus

PROVIDER: GSE178881 | GEO | 2022/01/10

REPOSITORIES: GEO

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