Gut Microbiome: A Promising Biomarker for Immunotherapy in Colorectal Cancer

Abstract

Research has been driven towards finding therapy predictive biomarkers for colorectal cancer (CRC) with a special interest in studying the gut microbiome. Gut microbiome acts not only as a barrier to prevent bacterial invasion and infection, but it also affects the efficacy of hematopoietic-cell transplantation, chemotherapy, and immunotherapy. Recently, immunotherapy, which potentiates the host immune system, has revolutionized cancer therapy in general and CRC treatment specifically by increasing the quality of life and the survival of a subset of patients with this disease. In immunotherapy, the gut microbiome plays an important role in cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blockade, programmed cell death protein 1 (PD-L1) mediation, and T cell stimulation. As such, this review will cover the role of gut microbiome in CRC, summarize approved immunotherapy treatments for CRC, and focus on the potential use of gut microbiome as a biomarker for immunotherapy.

Keywords: colorectal cancer; gut microbiome; immunotherapy.

Figure 1

Gut microbiome plays an essential role in response to cancer treatment. Specific bacteria in the gut microbiome influence response to chemotherapy (shown in yellow ovals), hematopoietic stem cell transplantation (shown in orange ovals), and immunotherapy (shown in blue ovals). Bacterial strains influencing immunotherapy do so by either inhibiting or enhancing programmed cell death protein 1 (PDL1) blockade, by stimulating T cell, or by stimulating cytotoxic T-lymphocyte-associated antigen (CTLA) blockade. Melanoma cells with no ring finger protein 5 (RNF5) and low unfolded protein response (UPR), which were administered B. Rodentium, also improved response to immunotherapy.

Figure 2

Fusobacterium correlated with poor outcome in high microsatellite instability (MSI-H) colorectal tumors by activating inflammatory mediators (interleukin (IL)1B, IL6, and IL8), secreting IL-12 and transforming growth factor β (TGF-β), and inhibiting natural killer cells and tumor infiltrating lymphocytes. TLR, Toll-like receptor.