Concurrent delivery of immune checkpoint blockade modulates T cell dynamics to enhance neoantigen vaccine-generated antitumor immunity.

ABSTRACT: Neoantigen vaccines aiming to induce tumor-specific T cell responses have achieved promising antitumor effects in early clinical trials. However, the underlying mechanism regarding response or resistance to this treatment is unclear. Here we observe that neoantigen vaccine-generated T cells can synergize with the immune checkpoint blockade for effective tumor control. Specifically, we performed single-cell sequencing on over 100,000 T cells and uncovered that combined therapy induces an 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, generation of neoantigen-specific T cells in the draining lymph node is required for combination treatment. Signature genes of this unique population are associated with T cell clonal frequency and better survival in humans. Our study profiles the dynamics of tumor-infiltrating T cells during neoantigen vaccine and immune checkpoint blockade treatments and high-dimensionally identifies neoantigen-reactive T cell signatures for future development of therapeutic strategies.

SUBMITTER: Liu L 

PROVIDER: S-EPMC9050907 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature