Journal of Clinical and Cellular Immunology
Open Access
ISSN: 2155-9899
ISSN: 2155-9899
Pawan Kumar and Sangeeta Bhaskar
Posters-Accepted Abstracts: J Clin Cell Immunol
Owing to their immunostimulatory properties, mycobacteria can counter the negative regulatory mechanisms employed by growing tumors, while inducing a potent antitumor immune response. Mycobacterium indicus pranii (MIP) is an atypical mycobacterial species possessing strong immunomodulatory properties. Therefore, we evaluated the immunotherapeutic potential of MIP in a mouse tumor model and examined the underlying mechanisms. It was observed that MIP therapy led to a significant tumor regression and enhanced the survival of tumor bearing mice. MIP promoted a tumor specific, TH1 type of immune response in tumor bearing mice. Higher NK cell and CTL cytotoxicity were observed in MIP-treated tumor bearing mice compared with PBS-treated control mice. MIP therapy also resulted in decreased levels of immunosuppressive CD4+FoxP3+ T regulatory cells in tumor mass and draining lymph node. Next, the role of dendritic cells and macrophages in mediating the MIP-induced antitumor immune response was analyzed. It was observed that MIP led to a significant production of proinflammatory cytokines and upregulation of co-stimulatory molecules by these cells. MIP-activated macrophages lysed the tumor cells in peroxynitrite-dependent manner. MIP promoted dendritic cell survival by inhibiting their apoptosis. MIPstimulated DCs promoted TH1 and TH17 polarization in naïve allogeneic T cells. TLR2 and/or TLR9 were found to play critical role in MIP-induced DC and macrophage activation. Comparable levels of tumor volumes in controls and MIP-treated MyD88 knockout mice demonstrated that the antitumor effects of MIP are mediated by TLRs. Further studies with TLR-knockout mouse strains showed that TLR2 played a key role in MIP-induced tumor regression.