The Negative Impact of Antibiotics on Outcomes in Cancer Patients Treated With Immunotherapy

A New Independent Prognostic Factor?

A. Elkrief; L. Derosa; G. Kroemer; L. Zitvogel; B. Routy


Ann Oncol. 2019;30(10):1572-1579. 

In This Article

The Gut Microbiome in Oncology

The human gut microbiota represents a complex and interconnected ecosystem composed by trillions of microorganisms living within the human gut. Through its close proximity with the immune system harboring along the GI tract, the microbiota–host relationship represents a key element influencing multiple aspects of whole-body homeostasis including the inflammatory and immune tonus. The gut microbiome has physiological implications in a wide variety of human pathologies ranging from neurological, psychiatric, gastrointestinal (GI), autoimmune to metabolic diseases.[15] Recent studies have contributed to the idea that the gut microbiome determines the so-called 'immune-cancer set point',[20,21] including the capacity of ICI to stimulate the immune system to kill cancer cells. The microbiota also plays an important role in carcinogenesis, as individual microbes play a role in the etiology of up to 20% of human malignancies. As demonstrated in murine models, bacteria can either promote or suppress the growth and metastatic dissemination of tumor cell growth.[22,23] Thus, the gut microbiota can exert pro-inflammatory and immunosuppressive functions as demonstrated in breast cancer bearers, causing a surge in gamma delta T cells secreting galectin 1 that stimulate MDSC.[24]

Further contributing to the hypothesis that the gut microbiome is intimately linked to cancer development is recent evidence that disruption of the gut microbiota can increase the frequency and risk of relapse of certain types of cancers.[25] This effect is not only limited to GI tract cancers such as gastric or colorectal carcinomas where this association is proportional to the number of ATB courses,[26] but also applies to non-GI sites such as breast,[27–29] lung,[30] prostate and bladder cancers.[31] Accordingly, the gut microbiome impacts the progression of tumors under chemotherapy,[32,33] as well in the context of allogeneic stem cell transplantation.[34,35] These findings indicate a broad effect of the intestinal microbiota on the development and progression of an array of distinct malignancies.