New Insights Into the Cancer-Microbiome-Immune Axis: Decrypting a Decade of Discoveries

Abstract

The past decade has witnessed groundbreaking advances in the field of microbiome research. An area where immense implications of the microbiome have been demonstrated is tumor biology. The microbiome affects tumor initiation and progression through direct effects on the tumor cells and indirectly through manipulation of the immune system. It can also determine response to cancer therapies and predict disease progression and survival. Modulation of the microbiome can be harnessed to potentiate the efficacy of immunotherapies and decrease their toxicity. In this review, we comprehensively dissect recent evidence regarding the interaction of the microbiome and anti-tumor immune machinery and outline the critical questions which need to be addressed as we further explore this dynamic colloquy.

Keywords: cancer; cancer immunotherapy; gut microbiome; immune system; microbiome-immune crosstalk; tumor microenvironment.

Figure 1

Mechanisms of microbial immunomodulation during tumor progression. Mucosal microbes can modulate the immune system locally or after translocating to the sites of growing tumors. Moreover, they are able to transmit their influences to distant sites using mediators like metabolites, cytokines, chemokines, toxins and vesicles. Microbes can either interact directly with immune cells or provide indirect adjuvant cues for immunomodulation. The consequent inflammation can be either pro-tumorigenic or anti-tumorigenic, with a diverse range of effects on the innate and the adaptive immune system. TLR, Toll like receptor; PRR, pattern recognition receptor; TME, tumor microenvironment; SCFA, short chain fatty acid; TIL, tumor infiltrating lymphocyte; NKT cell, natural killer T cell; MDSC, myeloid derived suppressor cell; TAM, tumor associated macrophage; MBL, mannose binding lectin; MAIT, Mucosal associated invariant T cells.