Unlock the Power of Diet to Supercharge Immunotherapy and Beat Cancer Faster!

The advent of immunotherapy has revolutionized cancer treatment, offering new hope for patients. However, the effectiveness of immunotherapy varies significantly. Diet, a fundamental lifestyle factor, plays a crucial role in influencing immunotherapy outcomes by modulating the body, gut microbiome, and metabolism. Specific diets, such as ketogenic and plant-based diets, have demonstrated potential in improving treatment response. This article explores the intricate relationship between diet and immunotherapy outcomes, examining the effects of diet on cancer treatment, the impact of different dietary regimens, and the influence of gut microbiome composition on treatment response.

Understanding Immunotherapy

Immunotherapy harnesses the body’s natural immune system to combat cancer. This approach encompasses a variety of methods, including targeted antibodies, vaccines, and viral therapies, often integrated with traditional treatments like surgery, chemotherapy, or radiation. The goal of immunotherapy is to restore or enhance the immune system’s ability to recognize and destroy cancer cells.

Immunotherapy is now recognized as one of five major types of cancer treatment, alongside surgery, radiation, chemotherapy and targeted therapy. Our immune system can find and destroy cancer cells. But sometimes cancer cells can hide from the immune system, allowing them to continue multiplying and spreading into other tissues. If cancer cells hide from the immune system and are not destroyed, it may affect the immune system’s ability to work properly. The idea of immunotherapy is to help restore the immune system’s ability to destroy cancer cells.

Immunotherapy treatment can be given intravenously (IV), in pills, in capsules or topically as a cream you rub into your skin. The method will depend on which type of cancer is being treated, and which type of immunotherapy is being used.

Some types of immunotherapies include:

Immune checkpoint inhibitors
T-cell transfer therapy
Immune system modulators
Monoclonal antibodies
Therapeutic vaccines
Cytokines
Nonspecific immune system modulators

So far, immunotherapy works best for specific sub-types of each of these types of cancers:

Melanoma (skin cancer)
Cervical
Lung
Skin
Breast
Brain
Prostate

The Importance of Healthy Eating During Immunotherapy

Healthy eating during immunotherapy offers numerous benefits, extending beyond enhancing the body’s response to treatment. During immunotherapy, nutritional needs may change, necessitating adjustments to ensure the body receives the essential nutrients required to stay strong and support healing.

Hydration: Staying well-hydrated is crucial during cancer treatment. In addition to water, hydrate with clear soups, fruit and vegetable juices, sports drinks, tea, milkshakes, and nutritional supplement drinks. It’s recommended to drink half of your body weight in ounces of fluid per day.
Protein Intake: Protein is essential for strengthening the immune system and promoting healing. Incorporate protein-rich foods into your diet, such as fish, poultry, lean red meats, low-fat dairy products, eggs, beans, lentils, nuts, and soy foods.
Calorie Consumption: You may require more calories than usual during cancer treatment to support your body’s energy needs. Focus on consuming nutrient-dense foods that provide essential vitamins and minerals along with calories.
Addressing Eating Challenges: Cancer treatment can sometimes cause eating challenges, such as mouth sores and throat irritation, making it difficult to swallow. In such cases, opt for softer, easier-to-swallow foods like thick, cold milkshakes, gelatin, ice pops, and ice cream.

By prioritizing hydration, protein intake, and nutrient-dense foods, you can support your body’s immune function and promote healing during immunotherapy.

Dietary Strategies to Enhance Immunotherapy Effectiveness

The Mediterranean Diet

A Mediterranean diet could enhance the effectiveness of immunotherapy in advanced melanoma patients. The study, conducted across multiple centers, emphasized the importance of dietary assessment for cancer patients undergoing immunotherapy. Alongside promoting overall response rates and survival, the Mediterranean diet was also linked to a lower risk of immune-related side effects. The Western diet, characterized by excessive consumption of processed and refined foods, has been linked to elevated inflammation levels. In contrast, diets rich in fruits, vegetables, whole grains, and healthy fats, exemplified by the Mediterranean diet consistently exhibit associations with reduced inflammatory markers.

Plant-Based Diets

A plant-based diet is not only recommended to help reduce your cancer risk; it also has benefits during cancer treatment. Plant-based means that most of the foods you consume will come from plants. “Plant foods with antioxidants and phytonutrients are especially good,” says Ebrus. Foods high in phytonutrients tend to be colorful, like the colors of the rainbow. Healthy fats help reduce inflammation in the body. You can get healthy fats by consuming foods, such as avocado, olive oil, cashews and walnuts. “We also recommend eating some lean animal protein, such as chicken, fish and turkey as well as plant-based proteins like beans, lentils and tofu,” says Ebrus.

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Ketogenic Diet

The ketogenic diet (KD) involves obtaining the majority of energy from fat (~75-90% fat) rather than carbohydrates (CHO),in contrast to the typical Western diet (55% CHO, 30% protein, 30% fat) According to the concept promoting KD in cancer therapy and prevention, reducing carbohydrate intake deplets ATP in cancer cells, while normal cells utilize ketone bodies as an energy substrate. A KD has been observed to lower glucose levels, thereby reducing lactate production by glycolytic cancer cells. Lactate serves as an inhibitor of dendritic cell maturation, hinders NK cell function, thereby limiting innate immunity effectors, and acts as a regulator of gene expression, including NCR1, which encodes a receptor activating NK cells. KD has been found to increase the CD4 + T-cell population and decrease Tregs in animals compared to controls. Additionally, Tregs from KD-fed animals produced less IL-10 when stimulated with tumor cells. KD has emerged as a potential adjuvant in cancer immunotherapy, positively impacting ICI responsiveness. By modulating the expression of immune checkpoint molecules like CTLA-4 and PD-1 on tumor-infiltrating lymphocytes and PD-L1 on tumor cells, KD may enhance ICI-based therapy effectiveness Ferrere et al. study, on mice exhibiting enhanced responses to anti-PD-1 therapy when fed a KD, suggest that it may amplify the anticancer effects of PD-1 blockade, underscoring the impact of diet on the effectiveness of immunotherapy. 3-Hydroxybutyrate, the principal ketone body, has been shown to induce T-cell-dependent tumor growth retardation in aggressive tumor models, even when standard therapies fail. KD can complement anticancer treatments like immunogenic chemotherapy and immunotherapy, aiming to boost the immune response, minimize the necessity for numerous treatment cycles, and improve the chances of achieving complete remission.

High-Fiber Diets

High-fiber diets may improve the effectiveness of some forms of immunotherapy. In an observational study of people treated for melanoma with immune checkpoint inhibitor immunotherapy, after adjusting for clinical factors, each additional five grams of dietary fiber was associated with a 30 percent lower risk of cancer progression or death. Consuming fibrous foods as prebiotics in the gut influences mucosal immune functions, reducing the risk of enteric inflammation by elevating anti-inflammatory cytokines and decreasing proinflammatory cytokines and the systemic immune response. Undigested food can be converted into short-chain FAs (SCFA), like butyrate, which the gut absorbs, alleviating inflammatory disorders by boosting T-regulatory cell (Treg) numbers and reducing IFN-γ levels. A fiber-rich diet proves beneficial when using ICIs, likely due to the increased SCFAs that stimulate immune cell differentiation and function The beneficial effects of dietary fiber consumption stem from its physical, immunomodulatory, and prebiotic properties. Nonfermentable fiber in the diet increases fecal bulk, effectively diluting carcinogenic substances in the gastrointestinal tract. Additionally, fermented dietary fiber reduces fecal pH, diminishing the production of carcinogenic compounds from bile acid metabolism by intestinal bacteria.

The Gut Microbiome and Immunotherapy

The gut microbiome, which is made up of bacteria and other microbes that live in the gut, is strongly related to the body’s immune system. What you eat influences the types of microbes that make up your gut microbiome.

Studies on mouse models have revealed significant shifts in gut microbiome composition following immunotherapy. For instance, mice treated with a single injection of CTLA-4 antibody demonstrated notable alterations, including an increase in Clostridiales and a decline in Bacteroidales and Burkholderiales The efficacy of CTLA-4 blockade was significantly reduced in mice treated with broad-spectrum antibiotics In the case of PD-1 blockade, the gut microbiome profiling showed an increase in Bifidobacterium species.

Managing Common Side Effects Through Diet

During immunotherapy, certain foods may exacerbate common side effects, such as dry mouth or mouth irritation. Diet changes can help manage your side effects, but you may also need medicine. If you’re prescribed medicine, be sure to take it as advised by your healthcare provider.

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Appetite Loss: Eat by a schedule. Choose calorie and protein dense foods. Avoid drinking large amounts (more than 4 to 6 ounces) of liquids with your meals. Move around when possible.
Nausea and Vomiting: Try not to skip meals. Sip on liquids throughout the day.
Constipation: Drink plenty of liquids, at least 8 to 10 cups daily. Increase your physical activity.
Diarrhea: Drink plenty of liquids. Aim to have at least 1 cup of liquid after each loose bowel movement. Avoid high sugar, high fat, and spicy foods. Avoid foods and liquids made with sorbitol, xylitol, or mannitol sugar substitutes.
Dry Mouth: Rinse your mouth before and after meals. Use an alcohol-free mouthwash, such as Biotene®. Drink plenty of liquids throughout the day, at least 8 to 10 cups.
Mouth and Throat Sores: Cook foods until they are soft and tender. Avoid foods that may cause pain. Use extra sauces, broths, oils, butter and gravies. Rinse your mouth often. Use an alcohol-free mouthwash, such as Biotene®.
Taste Changes: Avoid protein foods with strong odors, such as beef and fish.
Early Satiety: Engage in light physical activity after eating as able.
Reflux: Your health care team may prescribe you medications to help manage your reflux.
Fatigue: Dietary supplements include vitamins, minerals, and herbal supplements.

Addressing Loss of Appetite

No appetite? Though you might not feel like eating, it's important to do what you can to maintain your calorie, protein and fluid intake during cancer treatment. Keep in mind that in some cases, such as advanced cancer, eating may not affect the outcome of your illness or treatment. Sometimes caregivers or family members can unintentionally add stress by pushing or trying to force you to eat certain foods. Eat small amounts more frequently. If you feel full after eating only a small amount, try eating small amounts throughout the day when you get the urge to eat. Schedule mealtimes. Eat more when you're hungry. Take advantage of the times when you feel your best to eat more. Limit fluids during meals. Liquids can fill you up and limit your intake of higher calorie foods. Create a pleasant mealtime atmosphere. Make meals more appealing. Avoid smells that make you sick. Pay attention to smells, as certain scents may decrease your appetite or bring on nausea. Keep snacks handy. Don't be too concerned that some of these options are high in cholesterol or fat. Have a bedtime snack. Try cold foods. Foods that are cold or at room temperature may be more appealing, particularly if strong smells bother you. Experiment with foods. Exercise to increase your appetite. Regular exercise may help stimulate your appetite. Try shakes and instant drink mixes. Nutritional supplement drinks, such as instant breakfast mixes and canned or powdered shakes, can provide a significant amount of calories and require little or no preparation. Make your own smoothies. Combine fruits and vegetables with yogurt, ice cream or milk to make your own smoothies. Choose the ingredients that are most appealing to you. During illness, treatment or recovery, your need for calories and protein may be greater than usual. Add butter or oils to foods. Use butter or margarine generously on potatoes, bread, toast, hot cereal, rice, noodles and vegetables and in soups. Spread peanut butter or other nut butters - which contain protein and healthy fats - on toast, bread, apple or banana slices, crackers, or celery. Use fruit canned in heavy syrup. It has more calories than does fresh or juice-packed fruit. Drink beverages that contain calories, such as fruit juice, lemonade, fruit-flavored drinks, malts, floats, soda pop, cocoa, milkshakes, smoothies and eggnog. Though some of these suggestions add more fat and sugar to your diet, this shouldn't be a concern since you're only adding the extra calories until you can get your appetite back on track. Protein is important for growth, health and repair of your body. If you've been ill, you may need extra protein. Make your own high-protein milk: Add 1/4 cup powdered milk to 1 cup whole milk, or add 1 cup powdered milk to 1 quart whole milk. Drinking plenty of fluids also is key to helping your body during treatment. Try to choose drinks that contain calories. If your loss of appetite is keeping you from eating well for more than a few days, you might consider asking your doctor about taking a multivitamin.

The Role of Lipids and Inflammation

Chronic inflammation, impacting cancer development, can be influenced by diet. This type of inflammation may not cause noticeable symptoms in the way acute inflammation does, but it can contribute to various chronic conditions and diseases, like cancer Studies indicate that a vegetables-rich diet is linked to a reduced inflammatory profile. The impact of vegetable consumption on lymphocyte counts is mediated by the bacterial genus Collinsella, which tends to increase with the intake of processed foods The dietary composition of FAs influences cytokine production. Saturated FAs minimally impact cytokine production, whereas polyunsaturated FAs hinder the production of Th1-type cytokines, known for eliciting proinflammatory responses. To establish a distinct classification of foods negatively affecting the body’s inflammatory processes, the Dietary Inflammatory Index (DII) was created. Introduced in 2013, the DII was formulated with the goal of developing a literature-derived, population-based index to assess the inflammatory potential of diverse diets Incorporating foods with lower DII scores, such as fruits, vegetables, whole grains, lean proteins, healthy fats, and specific spices, can effectively reduce systemic inflammation and mitigate the risk of cancer development. Interestingly, patients with a high body mass index (BMI) were found to have better responses to anti-PD-1/PD-L1 therapy than those with lower BMI. However, while some anticancer immunotherapies benefit from very low carb or ketogenic diets, high-fat diets may worsen therapy outcomes When considering the role of lipids as metabolites, it is essential to recognize their diverse functions in carcinogenesis, encompassing structural roles in membrane formation and energy production. The accumulation of lipid droplets has been positively linked to the advancement of various cancers, including melanoma and pancreatic cancer. A patient’s nutritional state, especially their fat intake, significantly affects how they respond to anticancer therapy. High-fat diets and high-fat diet-induced obesity have been shown to accelerate tumor growth.

Recent Research and Future Directions

Over the past decade (2013-2023), there has been a noticeable increase in clinical research integrating immunotherapy, diet, and supplementation in cancer therapy. Recent advancements, including single-cell sequencing, high-dimensional cytometry, and CRISPR‒Cas9 gene editing, have revolutionized immunology research, allowing in-depth exploration of immune cell heterogeneity and function. Also, Raman imaging, a label-free and noninvasive technique combined with chemometrics methods, is a potent approach for analyzing dietary-induced biochemical and morphological changes in immune cells (e.g., macrophages, lymphocytes).

Researchers are looking at how diet and physical activity may improve the effectiveness of immunotherapy. AICR is funding some of this work.

Intermittent fasting

Periodic cycles of fasting and periods of normal nutrition have been tested in mouse models of cancer treated with immunotherapy. These studies suggest some improvements in treatment effectiveness and reduction in heart damage that immunotherapy may cause. Human studies of this type of diet for use with immunotherapy are extremely limited and more research is needed to understand how effective they may be and how safe they are in people at risk of malnutrition due to cancer.

Physical activity

Being active may enhance the effectiveness of immunotherapy. Research is in progress on how individual exercise sessions and long-term lifestyle with physical activity might each improve response to several types of cancer immunotherapy. Researchers are looking into the types, intensity and amount of physical activity that are most effective in supporting cancer immunotherapy treatments.

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