The Role of the Gut Microbiome in Cancer Immunotherapy: Current Knowledge and Future Directions

Abstract

Cancer immunotherapy is a treatment modality that aims to stimulate the anti-tumor immunity of the host to elicit favorable clinical outcomes. Immune checkpoint inhibitors (ICIs) gained traction due to the lasting effects and better tolerance in patients carrying solid tumors in comparison to conventional treatment. However, a significant portion of patients may present primary or acquired resistance (non-responders), and thus, they may have limited therapeutic outcomes. Resistance to ICIs can be derived from host-related, tumor-intrinsic, or environmental factors. Recent studies suggest a correlation of gut microbiota with resistance and response to immunotherapy as well as with the incidence of adverse events. Currently, preclinical and clinical studies aim to elucidate the unique microbial signatures related to ICI response and anti-tumor immunity, employing metagenomics and/or multi-omics. Decoding this complex relationship can provide the basis for manipulating the malleable structure of the gut microbiota to enhance therapeutic success. Here, we delve into the factors affecting resistance to ICIs, focusing on the intricate gut microbiome–immunity interplay. Additionally, we review clinical studies and discuss future trends and directions in this promising field.

Biological mechanisms of resistance to immune checkpoint inhibitors and overcoming this resistance: Challenges in medical oncology

“…The consequence of dysbacteriosis can potentially be not only colorectal cancer but also hepatocellular carcinoma and breast cancer. A healthy gut microbiota is thought to increase the levels of effector T cells, upregulate MHC-II, and activate dendritic cells (Kiousi et al, 2023).…”