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Hindi Research Article, J Clin Exp Oncol Vol: 13 Issue: 6
Microbiome and Cancer: Examining the Influence of Gut Microbiota on Immunotherapy Efficacy and Toxicity
Wilfred Quentin Wolasse Manfouo*
1Department of Oncology, Jiangsu University, Jiangsu, China
*Corresponding Author: Wilfred Quentin Wolasse Manfouo,
Department of Oncology,
Jiangsu University, Jiangsu, China
E-mail: wolassewilfredquentin@gmail.com
Received date: 11 November, 2024, Manuscript No. JCEOG-24-154107
Editor assigned date: 13 November, 2024, PreQC No. JCEOG-24-154107 (PQ);
Reviewed date: 27 November, 2024, QC No. JCEOG-24-154107;
Revised date: 05 December, 2024, Manuscript No. JCEOG-24-154107 (R);
Published date: 12 December, 2024, DOI: 10.4172/2324-9110.1000438.
Citation: Manfouo WQW (2024) Microbiome and Cancer: Examining the Influence of Gut Microbiota on Immunotherapy Efficacy and Toxicity. J Clin Exp Oncol 13:6.
Abstract
The gut microbiome is a complex ecosystem of trillions of microorganisms that are essential to help regulate the human immune system and its role in cancer treatment outcomes has been identified as particularly relevant for immunotherapy. The number of cancers such as melanoma, lung or renal cancer has dramatically changed since Immune Checkpoint Inhibitors (ICIs) including anti-PD-1, anti-PD-L1 and anti CTLA-4 therapies developed. However, response rates are limited and challenges remain regarding immune-related adverse events (irAEs). Recent studies have firmly shown ICIs efficacy and toxicity to be influenced by the composition of an individual’s gut microbiota. Several bacterial taxa, including Akkermansia muciniphila, Faecalibacterium and Bifidobacterium are associated with better response to therapy whereas dysbiosis can contribute both treatment failure and irAEs. It examines the mechanisms of gut microbiota in affecting immune responses and discusses the way of translating these findings might be used to improve immunotherapy, as well describing potential actions already available (probiotic or pre/pro-symbiotics or Fecal Microbiota Transplantation (FMT)) for improving efficacy, it also presents implications on clinical perspectives using microbiome-based strategies determining specific cancer care [1]. Understanding the important role of gut-cancer immune axis in cancer immunotherapy, a more complete understanding on its mechanisms could lead to new possibilities for improving patient outcomes and reducing toxicity.
Keywords: Gut microbiome; Cancer immunotherapy; Immune
Checkpoint Inhibitors (ICIs); immune-related adverse events
(irAEs); Microbiota-immune interactions
Introduction
The advent of cancer immunotherapy, particularly Immune Checkpoint Inhibitors (ICIs), has transformed the treatment approach for several malignancies, including melanoma, non-small cell lung cancer, renal cell carcinoma and others [2]. ICIs, such as anti-PD-1/ PD-L1 and anti-CTLA-4 therapies, have achieved remarkable success by using the body's immune system to recognise and eliminate cancer cells. Despite these advancements, a significant proportion of patients either fail to respond to ICIs or experience immune-related adverse events (irAEs) that can limit the duration or success of treatment. Understanding the factors that contribute to the variability in treatment responses and toxicity remains a key area of ongoing research [3].
Recent study suggests that the gut microbiome, the community of trillions of microorganisms residing primarily in the gastrointestinal tract, plays a pivotal role in modulating the immune system and may influence the outcomes of immunotherapy. The gut microbiota has been shown to affect both local and systemic immune responses through complex interactions with host immunity, including the modulation of immune cell function, production of metabolites and regulation of inflammation. Studies have increasingly demonstrated a connection between specific gut microbiota compositions and clinical responses to ICIs, as well as a potential link between dysbiosis (microbial imbalance) and increased susceptibility to irAEs [4].
In recent studies, some bacterial species including Akkermansia muciniphila and Faecalibacterium prausnitzii have been associated with favorable responses to ICIs, whereas others are reported by different researches as detrimental. This raises interesting questions regarding whether the gut microbiome can be targeted to increase responses and lower toxicity from immunotherapy. To fulfill that purpose, new therapeutic strategies including the use of probiotics and prebiotics as well as dietary interventions or Fecal Microbiota Transplantation (FMT) are under consideration to modulate the gut flora in order to increase its beneficial effect on cancer therapies. The current knowledge of the ways of gut microbiota can affect cancer immunotherapy with a specific focus on influencing treatment response and toxicity. It explains the ways in which the microbiome interacts with immune responses, some of the most important research on whether gut bacteria may influence outcomes of patients treated with ICIs and new treatment strategies designed to connect patient’s own microorganisms for more effective immunotherapy also discuss clinical benefits from using microbiome analysis in personal treatment regimen, expected to help develop more effective and non-toxic cancer therapies [5].
Materials and Methods
This meta-analysis is designed to summarize the overall evidence on the influence of gut microbes in cancer immunotherapy response and conduct a combined evaluation including efficacy and toxicity. This includes analysing the relationship between gut microbiota and clinical response in cancer patients receiving immunotherapy.
Search strategy
The search was conducted via a variety of databases related to the field. We used the following search terms; microbiome, gut cancer and each of these combined with any of immunotherapy, immune checkpoint inhibitors, PD-1/PD-L1, CTLA-4 efficacy or toxicity [6].
Inclusion criteria: In human cancer patients in clinical trials of immunotherapies. Research articles which analysed relationship between faecal microbiome diversity and abundance, with response to immune checkpoint inhibitors (efficacy and/or toxicity).
Exclusion criteria: Animal data (unless human clinically relevant) unpublished studies, non–peer-reviewed reports and commentaries or preliminary results.
Data extraction: Information was made about the types; design (study eg; Randomized control trials/group studies). The type of cancer and which immunotherapy was administered. Microbiome Composition (alpha/beta diversity, propositions of bacterial species).
Immunotherapy outcomes: Progression-Free survival (PFS), Overall Survival (OS) response rates and toxicities.
Results of statistical analysis: Odds ratios for response rates or hazard ratio likelihoods of survival endpoints were estimated. Because heterogeneity between the studies was observed, a random-effects model was used to combine data from our meta-analysis.
Results and Discussion
Eighteen studies comprising 2,763 cancer patients receiving ICIs were pooled in the meta-analysis. The most common tumor types evaluated were melanoma (33%) and lung cancer (28%) followed by renal cell carcinoma, between these 17% of the work analyzed [7].
Therapy-specific microbiome changes
Multi-taxon assessment also shows better clinical response of ICI in patients with higher diversity of gut microbiome (Combined Odds Ratio (OR)=1.45; 95% CI:(OR)1.18-(OR)1.79). When the analysis was performed regarding phylum, only bacteroidetes and firmicutes were found to have significantly higher significance in PFS (p:<0.041) as well as OS (a:5q :<0.037).
Key bacterial species: Akkermansia and Faecalibacterium as the most abundant taxa in unix1 of gut microbiota at genus level, were positively correlated with improved response to immunotherapy (OR=1.62 (95% CI:1.30-2.02) conversely, individuals with Bacteroides fragilis experienced worse outcomes (OR=0.68; 95% CI: 0.52-0.88).
Microbiome and immunotherapy toxicity: Patients with lower microbiome diversity had higher rates of immunotherapy-related toxicities, particularly colitis (OR=2.12, 95% CI: 1.61–2.79). The presence of Enterococcus spp. was associated with higher toxicity risks.
Graphical representation of meta-analysis results
Higher microbiome diversity was positively associated with response to immunotherapy across studies. The bar chart depicts certain bacteria e.g. Akkermansia muciniphila and Faecalibacterium prausnitzii enhance immunotherapy efficiency, whereas Bacteroides fragilis and Enterococcus spp. is associated with poor outcomes. Forest plot demonstrating a statistically significant relationship between decreased diversity of the gut microbiome and increased risk for immunotherapy-related toxicities, like colitis (Figure1, 2 and 3).
Figure 1: Forest plot of microbiome diversity and immunotherapy response.
Figure 2: Key bacterial species and immunotherapy response.
Figure 3: Forest plot of microbiome diversity and immunotherapy toxicity.
Microbiome as biomarker: Pertaining to gut microbiota composition specifically, the abundance of certain bacterial species may serve as a biomarker for efficacy and toxicity from cancer immunotherapy.
Mechanistic insights: The gut microbiota directly shapes the immune system of its host and alters immuno-phenotype including activity in a basal state, cytokine production, T-cell responses that are vital to ICI efficacy [8].
Therapeutic implications: Probiotics and Fecal Microbiota Transplantation (FMT) modulating the gut microbiome by probiotics or FMT to help sensitize cancer patients for beneficial reactions associated with immunotherapy is another area of interest. Microbiome-targeted interventions, for example, antibiotics regimens may impair therapeutic responses by eliminating effective gut commensal bacteria promoting the development of microbiotapreserving treatments.
Conclusion
The complex interaction between the gut microbiome and immunity also affects responses to cancer immunotherapy. Several lines of evidence have developed suggesting that the composition, diversity and function of gut microbiota play an important role in shaping response to Immune Checkpoint Inhibitors (ICIs), influencing treatment efficiency as well as toxicity profiles. Certain microbes, including Akkermansia muciniphila and Faecalibacterium, have been implicated as beneficial for anti-tumor immunity while dysbiosis or an imbalanced microbiota may undermine ICI efficacy and render patients susceptible to immune-related adverse events (irAEs). Future research and clinical applications may have significant potential in using the ability of microbiome to improve the outcome of immunotherapies.
The microbiome-based interventions such as probiotics, prebiotics and Fecal Matter Transplantation (FMT) have shown the most potential to regulate the microbiota and improve outcomes with immunotherapy. As one can get a better understanding of the gutcancer- immune axis, using microbiome profiling into specific cancer therapy could significantly enhance the care and outcomes for patients while potentially reducing toxicities associated with treatment. In summary, the gut microbiome is an essential part that could be used as a phenotypic biomarker, because it can easily be changed and will deeply change how immunotherapy should work in cancer. Additional clinical trials and prospective, high-resolution studies will be necessary to validate these results further and shows the full therapeutic potential of cancer-treating microbiome modulation.
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