Immunotherapy is emerging as a promising avenue in oncology, gaining increasing importance and offering significant advantages over chemotherapy or radiotherapy. Dietary factors and habits can help or hinder the effectiveness of treatment. An article published in the journal ‘Cell Death and Disease’ examined recent studies and assessed the influence of foods, including vitamins, fatty acids, nutrients, micro- and macromolecules, dietary habits and diets, on the ability to modulate immune responses. [1].
The role of nutrition in immune cell function.
Diet plays a crucial role in the functioning of the immune system. Obesity and metabolic disorders can alter macrophage activation and lead to harmful inflammation. Dietary composition, particularly fatty acids, influence cytokine production. While saturated fatty acids have minimal effects on cytokine production, polyunsaturated fatty acids inhibit the production of Th1-type cytokines, known for their pro-inflammatory responses. A balance between Th1 and Th2 responses is crucial, particularly in cancers such as hepatocellular carcinoma.
The Dietary Inflammatory Index (DII) was developed to assess the inflammatory effects of foods. Consuming foods low in DII, such as fruits, vegetables, whole grains, lean proteins, healthy fats, and certain spices, may effectively reduce systemic inflammation and lower cancer risk.
Nutrition and diet strategies to improve the efficacy of immunotherapy
The composition of the diet significantly influences the functioning of the immune system and, consequently, also the effectiveness of immunotherapy.
High fiber diet
High-fiber foods have a positive effect on mucosal immune functions in the gut by increasing anti-inflammatory cytokines and decreasing pro-inflammatory cytokines. Undigested food can be converted into short-chain fatty acids (SCFAs), such as butyrate, which are absorbed in the gut and alleviate inflammatory disorders by increasing the number of regulatory T cells (Tregs) and interferon gamma (IFN-γ-). Reduced mirror. A high-fiber diet might also be beneficial when using immune checkpoint inhibitors (ICIs) such as pembrolizumab , nivolumab , or ipilimumab , since increased SCFA production can stimulate immune cell differentiation and function.
Ketogenic diet
This diet reduces glucose levels and thus reduces lactate production by glycolytic cancer cells. Lactate acts as an inhibitor of dendritic cell maturation and impairs NK cell function, which in turn limits innate immune effectors and acts as a regulator of gene expression, including NCR1, which encodes a receptor to activate NK cells.
Recent studies have shown that 3-hydroxybutyrate, the main ketone body, inhibits tumor growth even when standard therapies fail. This antineoplastic effect prevents the upregulation of PD-L1 on myeloid cells associated with immune checkpoint blockade, promotes the expansion of CXCR3-positive T cells, and leads to changes in the composition of the intestinal microbiota.
High fat diets
While some cancer immunotherapies benefit from very low-carbohydrate or ketogenic diets, high-fat diets (HFDs) may worsen therapeutic outcomes. Lipid droplet accumulation has been linked to the progression of several cancers, including melanoma and pancreatic cancer . In lymphoma, a shift toward lipid utilization is seen, resulting in decreased response to treatment.
Composition of the intestinal microbiota
The gut microbiota is sensitive to the components of the food we eat. The composition of the gut microbiota, in turn, decisively influences the response to immunotherapy. Specific changes in the gut flora have been found to increase the effectiveness of cancer immunotherapy or reduce treatment-related side effects.
Low protein diets
Low protein diets (LPD) result in the body receiving fewer amino acids than the tumor needs to grow. They may reduce tumor growth in some cancers by modulating the immune response and influencing signaling pathways in the tumor environment. The effect of protein restriction on tumor-associated macrophages (TAMs) is particularly interesting, as they switch to a tumoricidal and pro-inflammatory phenotype.
However, current evidence from experimental and epidemiological studies suggests that dairy protein consumption has benefits. For example, β-lactoglobulin, the main component of whey proteins, has immunostimulatory properties in addition to antioxidant properties. Lactoferrin has immunomodulatory effects on both innate and adaptive immune responses. Furthermore, lactoferrin can bind endotoxins, resulting in a reduction in the production of proinflammatory cytokines.
Calorie restriction and fasting
Nutritional interventions such as fasting or a calorie-restricted diet may improve the efficacy of immunotherapies by enhancing the immune response against tumors. This results in reduced infiltration of tumor-associated macrophages (TAMs), reduced tumor growth, and improved response to immunotherapies.
Calorie restriction involves reducing daily calorie intake by 10 to 50 percent, a strategy known to be effective in prolonging life and delaying age-related diseases.
The Fasting Mimicking Diet (FMD) is an alternative to traditional therapeutic fasting. It attempts to replicate the benefits of fasting with a controlled diet that has a specific macronutrient composition: low in protein, high in unsaturated fats, and low to moderate in carbohydrates. Preliminary results suggest that FMD is effective in reducing risk factors for aging, diabetes, cardiovascular disease, and cancer without significant adverse effects.
Supplements to enhance immunotherapies
Vitamin D is critical for immune regulation, reduces the risk of immune checkpoint inhibitor-induced colitis, and improves survival in certain cancers. It affects Treg and TH17 cells, as well as the NF-κB signaling pathway. Vitamin C modulates immune response and might enhance the effects of immune checkpoint therapies, although the exact mechanisms are still unclear. Polyphenols such as apigenin and EGCG exhibit antioxidant, antimicrobial, and anticancer properties that may inhibit key signaling pathways and produce synergistic effects with immunotherapies.
Impact of a high-salt diet on immunotherapy
High salt intake can have both positive and negative effects on immunotherapy. It promotes the conversion of myeloid-derived suppressor cells (MDSCs) into anti-tumor macrophages, which enhances anti-tumor T cell activity and immune response. However, excessive salt intake can also increase the metabolism of cancer cells, promote the spread of tumors, and cause inflammation and health problems such as high blood pressure and heart disease.
Holistic approach to cancer care
Lifestyle factors such as diet and exercise are becoming increasingly important in modulating the immune system. This highlights the importance of a holistic approach to cancer care that includes both prevention and treatment.
Fuente:
Golonko, A. et al. (2024): Dietary factors and their influence on immunotherapy strategies in oncology: a comprehensive review. Cell death and disease, DOI: 10.1038/s41419-024-06641-6.
