Vaccination with a shared oncogenic tumor-self antigen elicits a population of CD8+ T cells with a regulatory phenotype

Abstract

Cancer immunotherapy is a powerful tool for inducing antigen-specific antitumor cytotoxic T lymphocytes (CTLs). Next-generation strategies may include vaccination against overexpressed oncogenic tumor-self antigens. Previously, we reported vaccination against the oncogenic tumor-self antigen D52 (D52) was effective in preventing tumor growth. We recently reported that D52-vaccinated IL-10-deficient mice generated a significant memory response against tumor recurrence compared to wild-type mice and that vaccine-induced CD8+ IL-10+ T cells may possess regulatory function. Herein, we extended these studies by testing the hypothesis that D52-vaccine-elicited CD8+ IL-10+ T cells represent a distinct T cell population with a regulatory phenotype. C57Black/6J mice deficient in IL-10 or IFN-γ were vaccinated with the murine orthologue of D52; vaccination of wild-type (wt) mice served as a control for comparison. T cells were isolated from all three groups of vaccinated mice, and RNA was extracted from purified CD8+ T cells for deep sequencing and expression analysis. Chemokine receptor 8 (CCR8) and inducible co-stimulator (ICOS) were overexpressed in CD8+ T cells that produced IL-10 but not IFN-γ. These surface markers are associated with IL-10 producing CD4+ T regulatory cells thus supporting the possibility that CD8+ IL-10+ T cells elicited by D52 vaccination represent a unique regulatory T cell subset. The current phenotypic analyses of D52 vaccine elicited CD8+ T cells strengthen our premise that CD8+ IL-10+ T cells elicited by D52 tumor-self protein vaccination likely contribute to the suppression of memory CTL responses and inhibition of durable tumor immunity.

Preclinical support for tumor protein D52 as a cancer vaccine antigen

“…If so the CD8 IL-10 T cells may be inhibiting vaccine induced tumor immunity by secretion of IL-10, and production of perforin, and granzymes to either suppress or kill effector CD8 CTLs. 81 These molecular phenotypic analyses of mD52 DNA vaccine elicited CD8 T cells strengthen our hypothesis that the population of CD8 IL-10 T cells elicited by vaccination likely contribute to the suppression of memory CTL responses and inhibition of vaccine generated tumor immunity.…”

Untargeted metabolomics analysis reveals the metabolic disturbances and exacerbation of oxidative stress in recurrent spontaneous abortion

“…For instance, LR2 (Toll-like receptor 2) exhibits the ability to modulate immune responses by interacting with T cells within the adaptive immune system [ 44 ]. Additionally, CXCL8 (chemokine 8) is implicated in the chemotaxis and activation of T cells [ 45 ]. This study exclusively examined the correlation between metabolites and oxidative kinases in RSA.…”

A Mannose-Modified Lipid Calcium Phosphate Nanoparticle Vaccine Increased the Anti-Tumor Immune Response by Modulating the Tumor Microenvironment

“…Lipid calcium phosphate (CaP) nanoparticles have attracted much attention due to their unique advantages in vaccine delivery systems. Its design and preparation are essential for improving the bioavailability and immunological efficacy of vaccines [132][133][134][135]. Usually, the preparation process includes the solvent precipitation method and the co-precipitation method [136].…”