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Microbiota is considered an independent organ with the capability to modulate tumor growth and response to therapies. In the chemo-free era, the use of new immunotherapies, more selective and effective and less toxic, led to the extension of overall survival of patients, subject to their ability to not stop treatment. This has focused scientists' attention to optimize responses by understanding and changing microbiota composition. While we have obtained abundant data from studies in oncologic and hematologic patients receiving conventional chemotherapy, we have less data about alterations in intestinal flora in those undergoing immunotherapy, especially based on Chimeric Antigen Receptor (CAR) T-cells. Actually, we know that the efficacy of Programmed Cell Death 1 (PD-1), PD-1 ligand, and Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) is improved by probiotics rich in Bifidobacterium spp., while compounds of Bacteroidales and Burkholderiales protect from the development of the anti-CTLA-4-induced colitis in mouse models. CAR T-cell therapy seems to not be interfering with microbiota; however, the numerous previous therapies may have caused permanent damage, thus obscuring the data we might have obtained. Therefore, this review opens a new chapter to transfer known acquisitions to a typology of patients destined to grow.

New Frontiers about the Role of Human Microbiota in Immunotherapy: The Immune Checkpoint Inhibitors and CAR T-Cell Therapy Era