INTERNATIONAL CONGRESS OF
CancerGenetics
Integration of Systemic Metabolism and Immune Regulation: New Frontiers in Cancer Prevention and Therapy
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Faezeh Arghidash,1,*
1. Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Introduction: Emerging evidence underscores the critical influence of systemic metabolic health on tumor progression and the effectiveness of anti-cancer immune responses. Factors such as obesity, diet, and microbiome composition significantly modulate the tumor microenvironment and the immune system’s capacity to recognize and eradicate cancer cells (1, 2). Obesity, in particular, promotes chronic inflammation and alters immune cell landscapes, which can facilitate metastasis and impair immunosurveillance (2, 3). Concurrently, the gut microbiota and its metabolites, including short-chain fatty acids like butyrate, play essential roles in regulating immune cell activity and enhancing responses to immunotherapies such as PD-1 inhibitors (4-6). These insights suggest that systemic metabolic alterations are not only central to cancer development but also represent modifiable targets to improve therapeutic outcomes. As research progresses, integrating metabolic health considerations such as dietary interventions, microbiome modulation, and metabolic therapies into cancer prevention and treatment regimens holds great promise for advancing personalized medicine and optimizing patient responses (7-9). Ultimately, translating these findings into clinical practice will require carefully designed trials to develop tolerable and effective strategies that leverage systemic metabolic regulation to strengthen anti-tumor immunity and improve patient survival.
- Methods: The present study was conducted based on the review of published studies in PubMed, Scopus, and Web of Science, and all studies were reviewed until 2024.
- Results: Recent studies highlight that systemic metabolic changes profoundly influence tumor progression and immune responses against cancer. For example, the composition of gut microbiota has been shown to impact the efficacy of immune checkpoint inhibitors, with certain bacterial populations and metabolites like short-chain fatty acids (SCFAs) enhancing treatment responses (4, 5). Specifically, butyrate, a microbial metabolite, promotes anti-tumor immunity by modulating T cell receptor signaling and improving the effectiveness of PD-1 blockade therapies (5, 6). Conversely, systemic metabolic disturbances such as obesity and age-related metabolic byproducts like methylmalonic acid can facilitate tumor progression and metastasis by creating an immunosuppressive microenvironment (7, 10). Research indicates that dietary strategies like calorie restriction and fasting-mimicking diets can reprogram immune cell activity and metabolic pathways within tumors, potentially enhancing the efficacy of immunotherapies (11-13). Moreover, the metabolic state of immune cells including tumor-infiltrating lymphocytes can be shaped by tumor-derived metabolites like lactate, which suppress immune function but can also be targeted to restore anti-tumor activity (14, 15). Overall, these findings underscore the interconnectedness of systemic metabolism and immune competence, suggesting that interventions targeting metabolic pathways such as microbiome modulation, dietary modifications, and metabolic therapies could significantly improve cancer treatment outcomes and facilitate personalized approaches to cancer management.
- Conclusion: In summary, systemic metabolic states play a crucial role in regulating anti-tumor immunity and cancer progression. Understanding how metabolic factors and the microbiome influence immune responses offers valuable insights for developing novel therapeutic strategies. To effectively translate these findings into clinical practice, carefully designed trials are necessary to identify safe and effective dietary, exercise, and metabolic interventions that can enhance treatment outcomes and improve patient survival. Finally, integrating knowledge of systemic metabolism into cancer prevention and therapy can lead to more personalized and effective approaches for managing this disease.
- Keywords: Tumor-immune interactions, Metabolic reprogramming, Systemic metabolism, Metabolic heterogeneity in
