Association between the gut microbiota and patient responses to cancer immune checkpoint inhibitors (Review)

Abstract

Studies are increasingly investigating the association between the gut microbiota and the outcomes of immunotherapy in patients with cancer. Notably, certain studies have demonstrated that the gut microbiota serves a key role in regulating a patient's response to immunotherapy. In the present review, the potential associations between the gut microbiota, and cancer, host immunity and cancer immunotherapy are reviewed. Furthermore, the effects of fecal microbiota transplantation, antibiotics, probiotics, prebiotics, synbiotics, components of traditional Chinese medicine and various lifestyle factors on the gut microbiota and cancer immunotherapy outcomes are discussed. Certain dominant bacterial groups in the context of cancer immunotherapy and certain effective methods for optimizing immunotherapy by regulating the gut microbiota have been identified. Further investigation may enable the rapid conversion of these discoveries into practical products and clinically applicable methods.

Impact of the Gut Microbiota Balance on the Health–Disease Relationship: The Importance of Consuming Probiotics and Prebiotics

“…That is why the immune system of the intestinal mucosa is related to cancer, in which its interaction with gut microbiota is considered a key factor in the maintenance of homeostasis [68,128]. Due to this interaction, there is an effect on the inhibition of bacterial adhesion and colonization, as well as the induction of cell differentiation [129].…”

“…In this sense, microbial species such as Bacteroides fragilis induce the differentiation of T cells CD4+ to regulatory T cells (Treg cells) [130], which are capable of secreting large amounts of antiinflammatory cytokines, such as IL-10, and recognizing antigenic substances associated with the bacterial genera Clostridium and Bacteroides [131,132]. However, the intestinal microbiota not only has an immunomodulatory effect at the local level, but also the systemic level [128]. Metabolites produced by microorganisms enter the bloodstream and, therefore, affect the immune response in distant organs through interaction with TLCR [129].…”

“…Although the microorganisms of gut microbiota do not directly induce tumorigenesis, they could interact with the immune system to indirectly promote the proliferation of cancer cells [10]. Thus, a defective immune response increases the abundance of certain bacterial genera and triggers signaling pathways that lead to the transcription of oncogenes [10,128]. In addition to this, gut microbiota can indirectly promote cancer by inducing inflammation or immunosuppression through the production of cytokines [133,134].…”

“…Some bacterial species related to the development of colorectal cancer, such as Fusobacterium nucleatum, Peptostreptococcus anaerobius, and Bacteroides fragilis enterotoxigenic, have been identified [136]. Moreover, a lower probability of survival in patients with colon cancer has been associated with F. nucleatum abundance [137] due to the induction of chemoresistance, which activates autophagy [134], leading to treatment failure or disease recurrence [128]. The species mentioned above induce tumor proliferation [138], promote inflammation [139], protect the tumor from the mechanisms exerted by the immune system [140], and cause damage to host cell DNA [141].…”

Food, Nutrition, Physical Activity and Microbiota: Which Impact on Lung Cancer?

“…Indeed, preliminary data suggest that both lung and gut microbiota are modulators of the carcinogenic process and seems also to influence the efficacy of immunotherapy affecting the prognosis and survival of the disease. Conversely, profiling of the gut and lung microbiota might reveal dysbiotic signatures associated with delayed tumor outgrowth and favorable responses to immunotherapy [ 23 ].…”