Examining the Role of Microbiota-Centered Interventions in Cancer Therapeutics: Applications for Urothelial Carcinoma

Abstract

Modern advances in genomic and molecular technologies have sparked substantial research on the human intestinal microbiome over the past decade. A deeper understanding of the microbiome has illuminated that dysbiosis, or a disruption in the microbiome, is associated with inflammatory disease states and carcinogenesis. Novel therapies that target the microbiome and restore healthy flora may have value in dampening the immunopathologic state induced by dysbiosis. A narrative review of the literature on the use of microbiota-centered interventions (MCIs) was conducted. Several randomized clinical trials show that MCIs can augment response to immune checkpoint inhibitor (ICI) therapy in patients with metastatic cancer. Clinical trials have also demonstrated that modulation of the intestinal microbiome can enhance recovery and reduce infectious complications in the surgical management of colorectal adenocarcinoma. Overall, these major discoveries suggest future clinical applications of MCIs for a wide range of immune-mediated conditions. These results may also translate to improved patient outcomes in systemic immunotherapy for urothelial carcinoma as well as in patients recovering from radical cystectomy (RC), which is complicated by high infection rates. Further research is needed to evaluate the optimal bacterial composition of microbiota-centered therapies and the specific cellular changes that lead to improved tumor antigen recognition after microbiota-centered therapies.

The Role of Tumor and Host Microbiome on Immunotherapy Response in Urologic Cancers

“…Unprecedented improvement in progression-free and overall survival, especially in patients with advanced disease, has highlighted that drugs targeting cytotoxic T-lymphocyte antigen (CTLA-4) and programmed death/ligand 1 (PD-1/PD-L1) are valuable for disrupting tumor growth and spread [ 22 ]. In fact, accumulating evidence suggests that the microbiome can modulate the efficacy and toxicity of immunotherapy by augmenting certain signals in the highly dynamic tumor microenvironment [ 23 , 24 ]. Several studies have shown that microbiota-centered interventions can improve response to immunotherapy in non-genitourinary cancers such as melanoma, hepatocellular carcinoma, and colorectal carcinoma [ 25 – 28 ].…”