Mycobacterium indicus pranii therapy induces tumor regression in MyD88- and TLR2-dependent manner

Objectives: Mycobacterium indicus pranii (MIP) is an atypical mycobacterium species with potent antitumor efficacy. Macrophages and dendritic cells (DCs) are antigen-presenting cells, playing key roles in the activation of antitumor immunity. We have previously shown the potent activation of macrophages and DCs by MIP, which is mediated by MyD88-TLR2 signaling axis. In the present study, we further examined the role of MyD88 and TLR2 in MIP-mediated tumor regression. Results: Wild-type and MyD88^-/- mice were implanted with B16F10 tumor cells, treated with MIP or phosphate-buffered saline (PBS) and monitored for tumor growth. As expected, MIP therapy led to significant tumor regression in wild-type mice. However, antitumor efficacy of MIP was lost in MyD88^-/- animals. Both PBS-treated (control) and MIP-treated MyD88^-/- mice developed tumors with comparable volume. Since MyD88 relays TLR engagement signals, we analyzed the antitumor efficacy of MIP in TLR2^-/- and TLR4^-/- mice. It was observed that MIP therapy reduced tumor burden in wild-type and TLR4^-/- mice but not in TLR2^-/- mice. Tumor volume in MIP-treated TLR2^-/- mice were comparable with those in PBS-treated wild-type animals. These results implicated the MyD88-TLR2 signaling axis in the antitumor efficacy of MIP.