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The human microbiome is a key player in regulating human physiology and disease. There is now compelling evidence from preclinical and clinical studies suggesting that the gut microbiome plays a key role in affecting host immunity and therapeutic response in cancer. The landscape of microbiome-based therapy will be instrumental in providing therapeutic strategies for several disease states, including cancer immunotherapy.
Introduction Often referred to as our second genome, the microbiome comprises of over 1,000 species with 100 trillion microbes that include bacteria, fungi, viruses, and protozoa. In recent years, research in the microbiome has increased, particularly relating to its role in human health. The human microbiome has a complex ecosystem that is inextricably interlinked with our immune system and must stay balanced and nurtured to remain healthy. Since 70% of the immune system is located in the gut, where the microbiome resides, there are many benefits to the host, especially relating to immune homeostasis. It is now well established that several diseases, including metabolic, neoplastic, and psychiatric disorders, are influenced by microbiome composition. Microbial dysbiosis refers to how the microbiome influences organs that are in direct contact and those that are distally located. Although it is known that the gut microbiota may alter the efficacy of chemotherapy and radiation therapy for cancer, there is now accumulating evidence that the intestinal microbiota composition has a profound impact on influencing the therapeutic efficacy of immunotherapies. Human Microbiome and Cancer Immunotherapy Tumorigenesis is a multistep and complex process involving both genetic and epigenetic changes within the tumor cell in addition to supportive conditions within the tumor microenvironment (TME). Cancer immunotherapy is a novel biotherapy designed to enhance immune responses against cancer and spans a wide spectrum of immune modulation. Of all the immunotherapy drugs developed and utilized for cancer treatment immune checkpoint inhibitors (ICIs) are the most widely used and have shown impressive efficacy in several cancer types. Numerous studies have reported that the intestinal microbiota composition has a profound impact not only on the therapeutic efficacy of immunotherapies, but also the efficacy of conventional chemotherapy in combination with immunotherapy. The link between microbial composition and clinical response suggests a direct mechanistic influence on immunotherapy in cancer patients. Moreover, the mounting evidence linking the gut microbiome to immunotherapy efficacy indicates that this relationship is causal rather than correlative based on the preclinical and clinical evidence. In addition to its utility as a complementary predictive biomarker of treatment outcomes, interventional strategies manipulating the microbiome will likely enhance the therapeutic efficacy of ICI therapy. Other approaches include modulation of the dietary changes that promote beneficial or deprive detrimental bacteria of their required nutrients. For example, polyphenols and high fiber foods have been shown to promote antitumor immunity. Summary Accumulating evidence has demonstrated the importance of the gut microbiota in oncogenesis and the response to treatment modalities. As a result, microbiota modulation for effective anticancer therapeutics has emerged as a new strategy, particularly with respect to ICIs. A better understanding of the correlation between the tumor microenvironment and the host immune system will help mitigate the side effects of cancer immunotherapies. Future strategies of precision medicine integrating companion diagnostics with therapeutic tools, to both identify and modulate the microbiome, should facilitate enhanced therapeutic outcomes. References
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