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Therapeutic cancer vaccines are designed to increase tumor-specific T cell immunity. However, suppressive mechanisms within the tumor microenvironment (TME) may limit T cell function. Here, we assessed how the route of vaccination alters intratumoral myeloid cells. Using a self-assembling nanoparticle vaccine that links tumor antigen peptides to a Toll-like receptor 7/8 agonist (SNP-7/8a), we treated tumor-bearing mice subcutaneously (SNP-SC) or intravenously (SNP-IV). Both routes generated antigen-specific CD8 T cells that infiltrated tumors. However, only SNP-IV mediated tumor regression, dependent on systemic type I interferon at the time of boost. Single-cell RNA-sequencing revealed that intratumoral monocytes expressing an immunoregulatory gene signature (Chil3, Anxa2, Wfdc17) were reduced after SNP-IV boost. In humans, the Chil3 monocyte gene signature is enriched in CD16 monocytes and associated with worse outcomes. Our results show that the generation of tumor-specific CD8 T cells combined with remodeling of the TME is a promising approach for tumor immunotherapy.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9669246 | PMC |
| http://dx.doi.org/10.1016/j.cell.2022.10.006 | DOI Listing |
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