microorganisms that make up the human microbiome are helpful to our health, but a smaller number are potentially harmful. Accruing evidence suggests that the balance between helpful and potentially harmful microorganisms in the microbiome contributes to overall health, and an imbalance can contribute to a number of diseases, including cancer (730). Composition of the human microbiome is affected by genetics as well as lifestyle factors, such as diet, environment, and antibiotic use (731). An imbalanced microbiome can cause inflammation in the intestine and contribute to colorectal cancer (732,733). There is mounting evidence that an imbalanced microbiome can also modulate tumor formation, metastasis, and resistance to treatment (734-736). Research has shown that tumors also harbor microorganisms and the type of microorganism present in tumors can predict health outcomes (see Figure 21, p. 150) (737). For example, two recent studies, one examining 35 different types of cancer and the other investigating cancers of the lung and gastrointestinal tract, revealed that tumors have unique populations of fungi that can predict cancer-specific outcomes (738,739). Several studies point to the link between microbial composition and response to cancer treatment (740). Researchers have found that modulating the microbiome can boost the effectiveness of anticancer treatment. As one example, oral administration of a type of bacteria that is naturally present in the microbiome enhanced the antitumor activity of a PD-1-targeting ICI (741). Conversely, findings from a retrospective study show that the overall survival of patients who were taking antibiotics that alter the microbiome’s diversity prior to immunotherapy was negatively impacted (742). In another study, researchers found that patients with B-cell lymphoma who were not treated with antibiotics showed better clinical response to CAR T-cell therapy (743). There are many ongoing clinical trials investigating the role of the microbiome in cancer therapy (740). Some are modulating the microbiome as a way to reduce or prevent toxic side effects of cancer treatment, while others are combining modulation of the gut microbiome with immunotherapy to enhance the effectiveness of the latter. Findings from these studies have the potential to revolutionize future cancer treatment and care. Envisioning the Future of Cancer Science and Medicine AACR Cancer Progress Report 2023 151
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