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.