Exploring the emerging role of the microbiome in cancer immunotherapy

Abstract

The activity of the commensal microbiota significantly impacts human health and has been linked to the development of many diseases, including cancer. Gnotobiotic animal models have shown that the microbiota has many effects on host physiology, including on the development and regulation of immune responses. More recently, evidence has indicated that the microbiota can more specifically influence the outcome of cancer immunotherapy. Therapeutic interventions to optimize microbiota composition to improve immunotherapy outcomes have shown promise in mouse studies. Ongoing endeavors are translating these pre-clinical findings to early stage clinical testing. In this review we summarize 1) basic methodologies and considerations for studies of host-microbiota interactions; 2) experimental evidence towards a causal link between gut microbiota composition and immunotherapeutic efficacy; 3) possible mechanisms governing the microbiota-mediated impact on immunotherapy efficacy. Moving forward, there is need for a deeper understanding of the underlying biological mechanisms that link specific bacterial strains to host immunity. Integrating microbiome effects with other tumor and host factors regulating immunotherapy responsiveness versus resistance could facilitate optimization of therapeutic outcomes.

The lung microbiota: role in maintaining pulmonary immune homeostasis and its implications in cancer development and therapy

“…Although it has been demonstrated that GF mice have a similar level of B and T cells, conventional and CD103 + DCs and pDCs compared to normal mice [36,39], the lack of microbiota interferes with the correct development of the immune system [36,37]. Therefore, in these mice the immune system is quite immature, and the introduction of bacteria may induce an immune response that it is not superimposable with a "physiologic" inflammatory response [40,41]. Alterations in the immune response in these mice are also testified by the fact that they do not respond to different types of immunotherapy [42,43].…”

Gut metabolomics profiling of non-small cell lung cancer (NSCLC) patients under immunotherapy treatment

“…Furthermore, additional biomarkers are under investigations such as microsatellites [5], interferon signatures [6], T cell repertoire [7], major histocompatibility complex (MHC) status [8], and immune infiltrates [9]. In the context of multiple available biomarkers the changes occurring in the microbiota composition and metabolism have been proposed as a mechanism potentially affecting the response and the toxicity to immunotherapy [10].…”

Hyperprogression Under Immune Checkpoint-Based Immunotherapy—Current Understanding, The Role of PD-1/PD-L1 Tumour-Intrinsic Signalling, Future Directions and a Potential Large Animal Model

“…The microbiome is a well-known driver of inflammation and immune response. There is a body of evidence that gut microbiota impacts the outcomes of ICB treatment in melanoma patients [105][106][107][108][109][110], leading to increasing interest in therapeutic interventions into individual microbiome composition [105,109]. Furthermore, microbiota located at the site of the lesion seems to affect the history of the disease in resected pancreatic adenocarcinoma [111].…”