Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy

Abstract

Since the advent of successful cancer immunotherapy, biomarkers for predicting their efficacy before starting the treatment have been unmet medical need. Intestinal dysbiosis is a satellite syndrome of oncogenesis and stool metagenomics represents a non-invasive and increasingly costeffective approach with the potential to early diagnosis of cancer in different cancer types. The prognostic impact of antibiotic uptake and gut microbiota composition urged investigators to develop tools for the detection of gut dysbiosis for patient stratification and microbiota-centered "Gut OncoMicrobiome Signatures as next generation biomarkers for cancer immunotherapy" by Thomas, Fidelle, Routy et al. invited by NATURE REV CLIN ONCOL (NRCO-22-063V1) 01/20/23 clinical interventions. This review will outline that cancer patients share several Gut OncoMicrobiome Signatures (GOMS) with individuals suffering from seemingly unrelated chronic inflammatory disorders across various histotypes that instead tend to be different from the microbiome profiles of healthy individuals. This review presents the largest integrative metaanalysis of GOMS patterns associated with clinical benefit or resistance to immune checkpoint inhibitors (ICI) across 808 patients with cancer. We will discuss metabolic and immunological surrogate markers of gut dysbiosis and practical guidelines to incorporate GOMS in decision making for prospective clinical trials in immuno-oncology. Key points • Intestinal dysbiosis is a satellite manifestation of oncogenesis • Cancer patients share gut microbiome signatures with individuals suffering from seemingly unrelated diseases • Gut OncoMicrobiome signatures (GOMS) share profile commonalities across cancer histotypes • GOMS represent a non-invasive cost-effective promising approach to early diagnosis of cancer in different cancer types • Links between gut dysbiosis and microbial tissue colonization or infection offer new prospects of etiology, prevention and therapeutic intervention in distinct cancers such as PDAC or urothelial cancers • GOMS are candidate predictors of resistance to immune checkpoint inhibitors

Aging and cancer

“…Contrasting with the healthy (eubiotic) state, gut dysbiosis is characterized by an increase in the abundance of harmful microbial species coupled to a relative decrease of useful microbes. Importantly, multiple non-malignant age-associated diseases are coupled with similar shifts in the gut microflora as are cancers located outside of the gastrointestinal tract [ 47 ]. Experiments showing that the microbiota from young mice, as well as specific health-associated bacterial strains (such as Akkermansia muciniphila ), can enhance the lifespan of mice with progeria, suggest a causal implication of dysbiosis in aging [ 48 ].…”

Role of the gut microbiota in tumorigenesis and treatment

“…A distinctive characteristic of CRC is its close association with the gut microbiota, which constitutes an integral component of the tumor microenvironment 20 , 77 . The gut microbiota in patients with CRC has been extensively investigated, making it arguably the most exemplary illustration of the role played by the gut microbiota in cancer 78 . The initial evidence supporting the involvement of the gut microbiota in CRC emerged in 1975 when both germ-free and conventional mice were administered 1,2-dimethylhydrazine.…”

“…Research indicates that the gut microbiota plays a significant role in the initiation, progression and treatment of cancers such as BC 44 , CRC 78 , and HCC 129 , 131 . The main way to regulate the gut microbiota mentioned above is by increasing the abundance of beneficial bacteria, aiming to prevent cancer initiation and aid in cancer treatment.…”

Microbiome bacterial influencers of host immunity and response to immunotherapy

“… 134 The integrity of the intestinal barrier is crucial, and its impairment is linked to the development of cancer. 135 Therefore, due to the various immunomodulatory effects of C. aerofaciens , further explorations are required to identify the significance of this bacterium on ICI activity.…”