Induction of CD4+ and CD8+ anti-tumor effector T cell responses by bacteria mediated tumor therapy

Facultative anaerobic bacteria like E. coli can colonize solid tumors often resulting in tumor growth retardation or even clearance. Little mechanistic knowledge is available for this phenomenon which is however crucial for optimization and further implementation in the clinic. Here, we show that intravenous injections with E. coli TOP10 can induce clearance of CT26 tumors in BALB/c mice. Importantly, re-challenging mice which had cleared tumors showed that clearance was due to a specific immune reaction. Accordingly, lymphopenic mice never showed tumor clearance after infection. Depletion experiments revealed that during induction phase, CD8(+) T cells are the sole effectors responsible for tumor clearance while in the memory phase CD8(+) and CD4(+) T cells were involved. This was confirmed by adoptive transfer. CD4(+) and CD8(+) T cells could reject newly set tumors while CD8(+) T cells could even reject established tumors. Detailed analysis of adoptively transferred CD4(+) T cells during tumor challenge revealed expression of granzyme B, FasL, TNF- and IFN- in such T cells that might be involved in the anti-tumor activity. Our findings should pave the way for further optimization steps of this promising therapy. What's New? Certain types of bacteria naturally home to and invade tumors, where they accumulate and ultimately induce tumor shrinkage. How bacteria act to reduce tumors, however, is still unknown. The work presented here shows that intravenous administration of E. coli to mice bearing CT26 colon carcinomas results in the induction of an immune response involving tumor-specific cytotoxic CD4+ and CD8+ T cells. CD4+ and CD8+ T cells effected neoplasia clearance. The findings could have implications for the design of therapeutic strategies that enhance the immune-inductive, cancer-fighting potential of bacteria.