Data for: Cytosolic bacterial pathogens activate TLR pathways in tumors that synergistically enhance STING agonist cancer therapies

Bacterial pathogens that invade the eukaryotic cytosol are distinctive
tools for fighting cancer, as they preferentially target tumors and can
deliver cancer antigens to MHC-I. Cytosolic bacterial pathogens have
undergone extensive preclinical development and human clinical trials, yet
the molecular mechanisms by which they activate innate immunity in tumors
are unclear. We report that intratumoral delivery of phylogenetically
distinct cytosolic pathogens, including Listeria, Rickettsia, and
Burkholderia species, elicited anti-tumor responses in established, poorly
immunogenic melanoma and lymphoma in mice. We were surprised to observe
that although the bacteria required entry to the cytosol, the anti-tumor
responses were largely independent of the cytosolic sensors cGAS and STING
and instead required TLR signaling. Combining pathogens with STING
agonists elicited profound, synergistic anti-tumor effects with complete
responses in >80% of mice after a single dose. Small-molecule TLR
agonists also synergistically enhanced the anti-tumor activity of STING
agonists. The anti-tumor effects required RAG2 but not interferon
signaling. Mice cured from the combination therapy developed immunity to
cancer rechallenge that required CD8+ T cells. Together, these data
provide a framework for enhancing the efficacy of microbial cancer
therapies and small-molecule innate immune agonists, via the co-activation
of STING and TLRs.