Cellular mechanisms underlying beneficial versus detrimental effects of bacterial antitumor immunotherapy

Abstract

SummaryListeria monocytogenesengineered to express tumor antigens as a cancer vaccine has yielded mixed results. Here, we utilized an attenuated strain ofListeria(ΔactA, Lm) that does not express tumor antigen to explore the immunological response toListeriaitself in the context of intravenous (IV), intratumoral (IT), or a combination of IV+IT administration into tumor-bearing mice. Unexpectedly, we found thatLmpersisted in tumors of immune competent mice, regardless of the administration route. While ITLmalone led to the recruitment of immunosuppressive immune cells that promoted tumor growth, IVLmfollowed by ITLmcontrolled tumor growth. IVLmvaccination generated a pool of anti-Lmcytotoxic CD8 T cells that killedLm-infected non-tumor cells to control tumor growth. Our findings reveal a differential impact of ITLmadministration on tumor progression that depends on the presence of anti-LmCD8 T cells, rather than antitumor CD8 T cells, for antitumor therapeutic efficacy.