Abstract

Simple SummaryMicrobiota plays a fundamental role in the induction, training and function of the human immune system. The interactions between microbiota and immune cells have consequences in several settings, namely in carcinogenesis but also in anticancer activity. Immunotherapy, already widely used in the treatment of several solid cancers, modulates the action of the immune system, promoting antitumour effects. Recently, there has been a growing interest in studying the microbiota composition as a possible modulator of the tumour microenvironment and consequently of the response to certain therapies such as immunotherapy.The tumour microenvironment (TME) comprises a complex ecosystem of different cell types, including immune cells, cells of the vasculature and lymphatic system, cancer-associated fibroblasts, pericytes, and adipocytes. Cancer proliferation, invasion, metastasis, drug resistance and immune escape are all influenced by the dynamic interaction between cancer cells and TME. Microbes, such as bacteria, fungi, viruses, archaea and protists, found within tumour tissues, constitute the intratumour microbiota, which is tumour type-specific and distinct among patients with different clinical outcomes. Growing evidence reveals a significant relevance of local microbiota in the colon, liver, breast, lung, oral cavity and pancreas carcinogenesis. Moreover, there is a growing interest in the tumour immune microenvironment (TIME) pointed out in several cross-sectional studies on the correlation between microbiota and TME. It is now known that microorganisms have the capacity to change the density and function of anticancer and suppressive immune cells, enabling the promotion of an inflammatory environment. As immunotherapy (such as immune checkpoint inhibitors) is becoming a promising therapy using TIME as a therapeutic target, the analysis and comprehension of local microbiota and its modulating strategies can help improve cancer treatments.

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