Training the microbiota to increase immune checkpoint blockade and to reduce toxicity.

ABSTRACT

There is no doubt that immunotherapy, particularly immune checkpoint blockade (ICB), has drastically improved treatment of metastatic cancer patients. Microbiota composition has been proposed to be one of the reasons for failure or success. ICB works via the activation or reactivation of T cells that are "switched off" by tumor cells or by the tumor microenvironment. Even advanced metastatic disease, previously considered as untreatable, can benefit from cancer immunotherapy. However, still a good proportion of patients does not respond to therapy or acquires resistance during treatment. Some genera or species of bacteria have been associated with treatment response or toxicity, but as the composition of the microbiota is not static, rather, it is very dynamic there is promise that by changing the microbiota composition, or by harnessing the microbiota 'secrete' tricks, one can improve treatment efficacy or reduce toxicity. Several players, including diet, prebiotics, probiotics, and postbiotics, have been proposed to shape the microbiota. In this minireview, we summarize very recent data on how to train the microbiota to increase ICB efficacy and reduce toxicity.