Cancer Letters

Cancer Letters

Volume 380, Issue 1, 28 September 2016, Pages 356-358
Cancer Letters

Commensal bacteria modulate the tumor microenvironment

https://doi.org/10.1016/j.canlet.2015.12.028Get rights and content

Highlights

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    Data reveal that the milieu of immune cells and factors in the whole host environment determine the fate of dysplastic and preneoplastic lesions toward carcinogenesis or regression.

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    Clinically silent gastrointestinal tract immune networks and commensal microbiota may impart healthful phenotypes or alternatively stimulate distant smoldering carcinogenic processes in the mammary and prostate glands.

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    Microbes may thus be determining the fate of the distal cancer microenvironment.

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    Taken together, these results suggest that exposures to bacteria may be used therapeutically for epigenetic control of resident immune cell populations combating cancer.

Abstract

It has been recently shown that gut microbes modulate whole host immune and hormonal factors impacting the fate of distant preneoplastic lesions toward malignancy or regression. This raises the possibility that the tumor microenvironment interacts with broader systemic microbial-immune networks. These accumulated findings suggest novel therapeutic opportunities for holobiont engineering in emerging tumor microenvironments.

Introduction

Accumulated cancer research has revealed that the tumor microenvironment contributes to neoplastic disease progression, invasion, and metastasis [1], [2], [3]. Recent findings in mice, however, take this notion further by showing that many tumors are less autonomous than previously thought. Intriguing data reveal that immune cells and other factors in the whole host environment determine the fate of dysplastic and preneoplastic lesions toward carcinogenesis or regression [4], [5], [6], [7], [8], [9], [10], [11]. This systemic modulation of neoplastic disease may be described as the “tumor-macroenvironment” [5]. In this context, the host microbiome is emerging as an important modulator of the tumor microenvironment even in extra-intestinal sites.

Section snippets

The whole host shapes the tumor microenvironment

Using Paget's “seed and soil” paradigm, where “seed” is a cancerous cell and “soil” is the tissue environment, the “soil” may either promote or hinder the carcinogenic process. Neoplastic outcomes appear to depend upon coinciding systemic immune-related events [1], [2], [3], [4], perhaps explaining why people commonly exhibit pre-neoplastic lesions throughout their body though they don't develop cancer [12]. Recognizing that human genes could be mutated up to 1010 times during an individual's

Commensal microbes help define the tumor environment

It follows that the immune system, the metabolic profile, and the psychological condition of the host are all influenced by the microbiome. These factors, which also affect each other at the whole organism level, are important determinants in carcinogenesis and tumor progression. In accordance with the ‘holobiont’ concept, it was recently introduced that the gut microbiome shapes whole host biology or ‘tumor macroenvironment’ impacting tumor growth [5], [6]. Although there is substantial

The hygiene hypothesis and cancer

The biological significance of bacterial exposures much earlier in mammalian life is now becoming more fully appreciated [15], [33], [34]. Indeed, the “hygiene hypothesis” concept links bacteria with good health [10], [35], [36]. Conversely, pathologies arise later in life after too few perinatal and infant microbe exposures [4], [33], [34], [35], [37]. Studies in mouse models show that early-life exposures to bacteria [10], [11] and sterile [lysis-killed] microbes are sufficient for later-life

Optimizing gut bacteria and host animal signaling to prevent cancer

Earlier evidence for microbe-immune interactions in cancer was provided more than a decade ago by Erdman et al. showing that immune-deficient Rag-knockout (KO) mice colonized with commensal bacteria exist in a chronic, smoldering pro-inflammatory and pro-tumorigenic proximal state [4]. By contrast, their wild-type immune-competent counterparts were resistant to neoplasms due to a competent adaptive immune system with potent anti-neoplastic properties [4]. Subsequent adoptive cell transfer

Conclusions

Taken together, these findings offer exciting new microbe-based avenues for developing personalized or population-based medicine strategies to decrease the risk of malignancy. As the tumor microenvironment concept first put cancer cells into context within a lesion [2], [3], the notion of tumor macroenvironment puts carcinogenesis into a whole-body context that extends beyond the mammalian host to microbial passengers we may choose to engineer for our therapeutic benefit.

Conflict of interest

No potential conflicts of interest were disclosed.

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