Recombinant <i>Listeria</i> promotes tumor rejection by CD8 ⁺ T cell-dependent remodeling of the tumor microenvironment

Abstract

Significance The development of therapeutic cancer vaccines using recombinant microorganisms has been pursued for many decades. However, the underlying mechanisms of therapeutic cancer vaccines remain unclear. Here we compare recombinant Listeria -based cancer vaccines to synthetic long peptide and adenovirus delivery systems for tumor antigens, and describe immunologic correlates of antitumor efficacy of Listeria -based cancer vaccines. Our results show that the profound antitumor efficacy requires tumor microenvironment (TME) remodeling that depends on tumor-specific CD8 + T cells induced by live-attenuated double-deleted Listeria monocytogenes expressing cognate tumor antigens. Together, this work highlights the importance of cognate tumor antigen expression by cancer vaccines and pinpoints the relationship between induced tumor antigen-specific immunity and the TME.