The role of gut microbiome in immune modulation in metastatic renal cell carcinoma

Abstract

Treatment of metastatic renal cell carcinomas (mRCC) has drastically improved since the advent of immunotherapy with immune checkpoint inhibitors (ICIs), with a significant proportion of patients achieving durable responses. While this has revolutionized treatment and improved outcomes for mRCC patients, a large subset of patients still does not respond to treatment with ICIs. Moreover, ICIs can induce various immune-related adverse events, limiting their use in many patients. Therefore, there is a need to identify the predictive biomarkers of both efficacy and toxicity associated with ICIs, which would allow for a more personalized approach and help with clinical decision-making. This review aims to explore the role of the gut microbiome in RCC to overcome primary resistance and predict response to treatment with ICIs. First, current therapeutic strategies and mechanisms of action of ICI therapies for RCC treatment will be reviewed. With the technological development of shotgun whole-genome sequencing, the gut microbiome has emerged as an exciting field of research within oncology. Thus, the role of the microbiome and its bidirectional interaction with ICIs and other drugs will be explored, with a particular focus on the microbiome profile in RCC. Lastly, the rationale for future clinical interventions to overcome resistance to ICIs using fecal microbiota transplantation in patients with RCC will be presented.

The negative effect of antibiotics on RCC patients with immunotherapy: A systematic review and meta-analysis

“…ATB treatment can primarily lead to the modification of the human microbiota, especially the gut flora. Akkermansia muciniphila is the species most strongly associated with good clinical outcomes in RCC patients with immunotherapy for its function of recruiting CD4 + cells and dendritic cells ( 37 ). And some species such as Bacteroides , Firmicutes , and Bifidobacterium can also increase the response to immunotherapy and are associated with better prognosis.…”

Renal cancer: signaling pathways and advances in targeted therapies

“… 284 , 285 Increasing evidence suggests that gut microbiota a key host factor associated with the response to ICI therapy in various solid tumors, including RCC. 286 A study analyzing baseline stool samples of patients prior to ICI therapy showed that greater microbial diversity was associated with clinical benefit from ICI therapy ( p = 0.001), and multiple species were associated with clinical benefit or lack thereof. 287 Antibiotic use resulted in lower ORR and shorter PFS with ICI treatment and adversely affected OS in patients treated with IFN or with VEGF ‐targeted therapies and prior cytokines.…”

Neurological adverse events associated with PD-1/PD-L1 immune checkpoint inhibitors

“…Microorganisms are also a promising research direction. Intestinal microbiota in feces is a potential biomarker for predicting the efficacy and prognosis of PD-1 inhibitors ( Deluce et al, 2022 ). Liu et al (2021) collected fecal samples from patients in a prospective study and found that Streptococcus , Paecalibacterium, and Stenotrophomonas were significantly more abundant in patients with severe irAEs, while Faecalibacterium and unidentified Lachnospiraceae were more abundant in patients with mild irAEs.…”