Tumor-Associated Microbiome: Where Do We Stand?

Abstract

The study of the human microbiome in oncology is a growing and rapidly evolving field. In the past few years, there has been an exponential increase in the number of studies investigating associations of microbiome and cancer, from oncogenesis and cancer progression to resistance or sensitivity to specific anticancer therapies. The gut microbiome is now known to play a significant role in antitumor immune responses and in predicting the efficacy of immune-checkpoint inhibitors in cancer patients. Beyond the gut, the tumor-associated microbiome-microbe communities located either in the tumor or within its body compartment-seems to interact with the local microenvironment and the tumor immune contexture, ultimately impacting cancer progression and treatment outcome. However, pre-clinical research focusing on causality and mechanistic pathways as well as proof-of-concept studies are still needed to fully understand the potential clinical utility of microbiome in cancer patients. Moreover, there is a need for the standardization of methodology and the implementation of quality control across microbiome studies to allow for a better interpretation and greater comparability of the results reported between them. This review summarizes the accumulating evidence in the field and discusses the current and upcoming challenges of microbiome studies.

Keywords: cancer; carcinogenesis; dysbiosis; gut microbiome; metagenomics; tumor microbiome.

Figure 1

Impact of tumor-associated and gut microbiomes in cancer. (A) Carcinogenesis: intratumor bacteria and/or viruses and their by-products can activate oncogenic pathways and promote cell growth and proliferation. (B) Antitumor immunity: chronic inflammation caused by the local microbiome could lead to an immunosuppressive tumor microenvironment through altered antigen presentation and Tregs and myeloid-derived immunosuppressive cell (MDSC) stimulation, ultimately impairing anti-tumor immune-responses. (C) Gut–tumor immune-mediated response: gut bacteria and their by-products can enhance CD8+ T cell-mediated antitumor responses via (1) cross-reactivity of shared bacteria and tumor antigens recognized by T cells in the gut; (2) activation of dendritic cells, which will lead to T cell priming and expansion; (3) local pro-inflammatory cytokines or other bacterial products entering systemic circulation along with activated T cells. (D) Resistance to anticancer therapies: intratumoral bacteria can alter the efficacy of certain chemotherapies by altering the metabolism or through generating resistance to radiotherapy through hypoxic mechanisms.

Figure 2

Challenges of microbiome studies in cancer.