Immunization with lentivector expressing HBV Ag markedly improves the tumor microenvironment and result in regression of established tumors (131.44)

Abstract

Abstract One of the main reasons for the limited antitumor efficacy of current tumor vaccines is the failure of immune effector cells inside the tumor environment due to the infiltration of immune suppressor cells and immune dysfunction of effector cells. In this study, we investigated if the immune suppressive tumor environment can be improved by lentivector immunization. We found that lentivector immunization could not only stimulate potent T cell responses against HBV surface Ag and cause tumor influx of effector T cells, but also markedly changed the tumor microenvironment. Immunization with lentivector induces strong proliferation of CD4 and CD8 T effector cells but does not increase the proliferation of Treg in the vaccine draining LN. More importantly, lentivector immunization profoundly increase proliferation of the CD4 Teff cells in the tumor lesions, resulting in more CD4 Teff cells accumulation in the tumor lesions and decrease of Treg ratio in the tumor. Analysis of the tumor environment showed that lentivector immunization can skew immune suppressive tumor environment to Th1 and Tc1 like environment, with marked increase of T-bet, IFNγ, Perforin, and granzyme in the tumor lesions. Lentivector HBV-S-lv immunized mice were completely protected from HBV positive B16 tumor cells (B16-S) challenge. Furthermore, established B16-S tumor can be eradicated by lentivector immunization.