Contribution of Aging, Obesity, and Microbiota on Tumor Immunotherapy Efficacy and Toxicity

Baiden-Amissah, Regina E. M.; Tuyaerts, Sandra

doi:10.3390/ijms20143586

Cited by 24 publications

(15 citation statements)

References 75 publications

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“…Additionally, the role of specific microbiota signatures and their interaction with other factors that produce dysbiosis (i.e., antibiotic use, aging, and obesity) is an area of active investigation (34)(35)(36).…”

Section: Gut Microbiome and Toxicity To Icpismentioning

confidence: 99%

The role of gut microbiome in modulating response to immune checkpoint inhibitor therapy in cancer

Naqash¹,

Kihn-Alarcón²,

Stavraka³

et al. 2021

Ann Transl Med

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Immunotherapy has led to a paradigm shift in the treatment of several cancers. There have been significant efforts to identify biomarkers that can predict response and toxicities related to immune checkpoint inhibitor (ICPI) therapy. Despite these advances, it has been challenging to tease out why a subset of patients benefit more than others or why certain patients experience immune-related adverse events (irAEs). Although the immune-modulating properties of the human gut bacterial ecosystem are yet to be fully elucidated, there has been growing interest in evaluating the role of the gut microbiome in shaping the therapeutic response to cancer immunotherapy. Considerable research efforts are currently directed to utilizing metagenomic and metabolic profiling of stool microbiota in patients on ICPI-based therapies.Dysbiosis or loss of microbial diversity has been associated with a poor treatment response to ICPIs and worse survival outcomes in cancer patients. Emerging data have shown that certain bacterial strains, such as Faecalibacterium that confer sensitivity to ICPI, also have a higher propensity to increase the risk of irAEs. Additionally, the microbiome can modulate the local immune response at the intestinal interface and influence the trafficking of bacterial peptide primed T-cells distally, influencing the toxicity patterns to ICPI. Antibiotic or diet induced alterations in composition of the microbiome can also indirectly alter the production of certain bacterial metabolites such as deoxycholate and short chain fatty acids that can influence the anti-tumor tolerogenesis. Gaining sufficient understanding of the exact mechanisms underpinning the interplay between ICPI induced anti-tumor immunity and the immune modulatory role gut microbiome can be vital in identifying potential avenues of improving outcomes to cancer immunotherapy. In the current review, we have summarized and highlighted the key emerging data supporting the role of gut microbiome in regulating response to ICPIs in cancer.

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Section: Gut Microbiome and Toxicity To Icpismentioning

confidence: 99%

The role of gut microbiome in modulating response to immune checkpoint inhibitor therapy in cancer

Naqash¹,

Kihn-Alarcón²,

Stavraka³

et al. 2021

Ann Transl Med

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show abstract

“…There are several lines of evidence to suggest that the myeloid-derived cell function is a finely tuned mechanism to control tumor growth. Specifically, both in local and hematopoietic niches, its crosstalk with the tumor cells as well as with exogenous stimuli, is based on the microbiota repertoire [39,40].…”

Section: Tailoring Immunotherapy In Real-life Clinical Practicementioning

confidence: 99%

“…Therefore, the combination of MSI-H and EMAST-positive CRCs with high TMB may identify the best patients to a candidate for immunotherapy [34]. The gut microbiome plays an important role in response to immunotherapy, as well [40]. Different bacterial strains may inhibit or enhance PD-L1, acting differently on T-cells and on CTLA-4 blockade.…”

Section: Immune-related Biomarkers In Solid Tumors: Prognostic Andmentioning

confidence: 99%

Targeting Immune-Related Biological Processes in Solid Tumors: We do Need Biomarkers

Pagni

Guerini-Rocco

Schultheis

et al. 2019

IJMS

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Immunotherapy has become the standard-of-care in many solid tumors. Despite the significant recent achievements in the diagnosis and treatment of cancer, several issues related to patients’ selection for immunotherapy remain unsolved. Multiple lines of evidence suggest that, in this setting, the vision of a single biomarker is somewhat naïve and imprecise, given that immunotherapy does not follow the rules that we have experienced in the past for targeted therapies. On the other hand, additional immune-related biomarkers that are reliable in real-life clinical practice remain to be identified. Recently, the immune-checkpoint blockade has been approved in the US irrespective of the tumor site of origin. Further histology-agnostic approvals, coupled with with tumor-specific companion diagnostics and guidelines, are expected in this field. In addition, immune-related biomarkers can also have a significant prognostic value. In this review, we provide an overview of the role of these biomarkers and their characterization in the management of lung cancer, melanoma, colorectal cancer, gastric cancer, head and neck cancer, renal cell carcinoma, urothelial cancers, and breast cancer.

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“…Inflammation is involved in the progression of cancers, including breast and colon cancer [4,6,9]. There is evidence that the composition of the microbiome affects cancer immunity and the response to cancer immunotherapy, as reviewed in [10]. The absence of specific microbes can be associated with the alteration of gut lymphoid tissue integrity [11].…”

Section: Introductionmentioning

confidence: 99%

Obesity Modulates the Gut Microbiome in Triple-Negative Breast Cancer

et al. 2021

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Triple-negative breast cancer (TNBC) is an aggressive, molecularly heterogeneous subtype of breast cancer. Obesity is associated with increased incidence and worse prognosis in TNBC through various potential mechanisms. Recent evidence suggests that the gut microbiome plays a central role in the progression of cancer, and that imbalances or dysbiosis in the population of commensal microbiota can lead to inflammation and contribute to tumor progression. Obesity is characterized by low-grade inflammation, and gut dysbiosis is associated with obesity, chronic inflammation, and failure of cancer immunotherapy. However, the debate on what constitutes a “healthy” gut microbiome is ongoing, and the connection among the gut microbiome, obesity, and TNBC has not yet been addressed. This study aims to characterize the role of obesity in modulating the gut microbiome in a syngeneic mouse model of TNBC. 16S rRNA sequencing and metagenomic analyses were performed to analyze and annotate genus and taxonomic profiles. Our results suggest that obesity decreases alpha diversity in the gut microbiome. Metagenomic analysis revealed that obesity was the only significant factor explaining the similarity of the bacterial communities according to their taxonomic profiles. In contrast to the analysis of taxonomic profiles, the analysis of variation of functional profiles suggested that obesity status, tumor presence, and the obesity–tumor interaction were significant in explaining the variation of profiles, with obesity having the strongest correlation. The presence of tumor modified the profiles to a greater extent in obese than in lean animals. Further research is warranted to understand the impact of the gut microbiome on TNBC progression and immunotherapy.

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Contribution of Aging, Obesity, and Microbiota on Tumor Immunotherapy Efficacy and Toxicity

Cited by 24 publications

References 75 publications

The role of gut microbiome in modulating response to immune checkpoint inhibitor therapy in cancer

The role of gut microbiome in modulating response to immune checkpoint inhibitor therapy in cancer

Targeting Immune-Related Biological Processes in Solid Tumors: We do Need Biomarkers

Obesity Modulates the Gut Microbiome in Triple-Negative Breast Cancer

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