Immunotherapy with guts: a review of microbial therapeutic adjuncts for immunotherapy in solid tumors

Background: Immunotherapy has transformed the management of some solid tumor types, but its impact has been limited to the subset of cancer patients who have “hot” or immunogenic tumors. Num2erous studies are based on strategies for turning “cold,” or immune-unresponsive, tumors into a “hot” state. The gut microbiome has emerged as a potential co-therapy for standard immune checkpoint inhibitors (ICIs) to achieve this goal. Recent approaches have primarily focused on the use of probiotics, microbial consortia, or fecal microbiota transplantations in combination with anti-PD-1 and anti-CTLA-4 antibodies. Methods: This review highlights the current status of microbiome modulation and its potential impact on clinical practice. Probiotics, such as CMB588, and microbial consortia have been selected following successful preclinical studies. These taxa may initiate T cell infiltration and are commonly found in the microbial profiles of individuals who have previously responded to immunotherapy. Results: Several trials with these therapies have had success and noted minimal safety concerns compared to monotherapy treatments. Fecal microbiota transplantation (FMT), originally used to treat Clostridium difficile infections, has also demonstrated promising results in increasing immune checkpoint inhibitor (ICI) efficacy across various cancer types and is being utilized in multiple ongoing trials. Conclusion: These therapeutics form the foundation for exciting possibilities in immunotherapy and improving patient outcomes.