Activation of Anti-Tumor Immune Response and Reduction of Regulatory T Cells with Mycobacterium indicus pranii (MIP) Therapy in Tumor Bearing Mice

Abstract

BackgroundRole of immune system in protecting the host from cancer is well established. Growing cancer however subverts immune response towards Th2 type and escape from antitumor mechanism of the host. Activation of both innate and Th1 type response is crucial for host antitumor activity. In our previous study it was found, that Mycobacterium indicus pranii (MIP) also known as M. w induces Th1 type response and activates macrophages in animal model of tuberculosis. Hence, we studied the immunotherapeutic potential of MIP in mouse tumor model and the underlying mechanisms for its antitumor activity.Methodology and Principal FindingsTumors were implanted by injecting B16F10 melanoma cells subcutaneously into C57BL/6 mice. Using the optimized dose and treatment regimes, anti-tumor efficacy of heat killed MIP was evaluated. In MIP treated group, tumor appeared in only 50–60% of mice, tumor growth was delayed and tumor volume was less as compared to control. MIP mediated immune activation was analysed in the tumor microenvironment, tumor draining lymph node and spleen. Induction of Th1 response and higher infiltration of immune cells in the tumor microenvironment was observed in MIP treated mice. A large fraction of these immune cells were in activated state as confirmed by phenotypic and functional analysis. Interestingly, percentage of Treg cells in the tumor milieu of treated mice was less. We also evaluated efficacy of MIP along with chemotherapy and found a better response as compared to chemotherapy alone.ConclusionMIP therapy is effective in protecting mice from tumor. It activates the immune cells, increases their infiltration in tumor, and abrogates tumor mediated immune suppression.

Mycobacterium indicus pranii and Mycobacterium bovis BCG lead to differential macrophage activation in Toll‐like receptor‐dependent manner

“…Encouraging results including lower tumour burden, higher immune cell infiltration in tumour mass, and higher T-cell and NK-cell cytotoxicity against tumour cells were observed in MIP-treated mice. 18 Macrophages are important components of the mononuclear phagocytic system, strategically located throughout the body to ingest and process foreign materials and to recruit other immune cells to the site of insult. M1 macrophages produce pro-inflammatory cytokines and reactive nitrogen intermediates, and offer protection against infectious diseases and neoplastic conditions.…”

Desmocollin-3 and Cancer

“…It induces DSC3 expression on immune cells and also induces Th1 type of immune response through TLR2 agonist activity [48]. Cadi-05 increases tumor infiltrating immune cells [49] and found useful in management of cancers as a monotherapy for small size tumors [49,50]. As combination therapy with checkpoint modulators, radiotherapy as well as chemotherapy, Cadi-05 improves outcome of large size tumors [51].…”

A key role of GARP in the immune suppressive tumor microenvironment

“…[2] Herein, inhibitory cell populations such as regulatory T cells (Treg), myeloid-derived suppressor cells (MDSC) and tolerogenic dendritic cells (tolDC), as well as inhibitory factors of the tumor itself play a major role. [3–5] Better understanding of inhibitory molecules and pathways regulating melanoma initiation and progression that could be used as therapeutic targets or biomarkers is needed.…”