Ag85B-ENO146-82 therapeutic vaccines enhance anti-tumor immunity by inducing CD8+ T cells and remodeling tumor microenvironment.

ABSTRACT

Lung cancer is the leading cause of cancer-related morbidity and mortality in China. However, the effect of traditional cancer treatment is limited. Herein, we designed a therapeutic cancer vaccine based on the tumor-associated antigen mENO1, which can prevent lung cancer growth in vivo, and explored the underlying mechanism of Ag85B-ENO146-82 therapy. Lewis lung carcinoma (LLC) tumor-bearing immunocompetent C57BL/6 mice that received Ag85B-ENO146-82 treatment showed antitumor effect. Further, we detected CD8+ T, CD4+ T in LLC-bearing C57BL/6 mice to understand the impact of Ag85B-ENO146-82 therapy on antitumor capacity. The Ag85B-ENO146-82 therapy induced intensive infiltration of CD4+ and CD8+ T cells in tumors, increased tumor-specific IFN-γ and TNF-α secretion by CD8+ T cells and promoted macrophage polarization toward M1 phenotype. Flow cytometric analysis revealed that CD8+ T effector memory (TEM) cells and central memory (TCM) cells were upregulated. qPCR and ELISA analysis showed that the expression of IFN-γ and TNF-α were upregulated, whereas of IL1ß, IL6 and IL10 were downregulated. This study demonstrated that Ag85B-ENO146-82 vaccine augmented antitumor efficacy, which was CD8+ T cells dependent. Our findings paved the way for therapeutic tumor-associated antigen peptide vaccines to enhance anti-tumor immunotherapy for treatment of cancer.