Radiation beam intersecting metabolic pathways, activating immune cells.

Cancer's Hidden Game: How Metabolism and Immunity Interact

Jordan Keane in Health & Wellness September 2025 • 5 min read.

"Uncover How Modulating Metabolism with Radiation Therapy Can Boost Host Immunity in the Tumor Microenvironment."

The battle against cancer is a complex interplay between tumor cells and the body’s immune system. Immunotherapy, a revolutionary approach that harnesses the power of the immune system to fight cancer, has shown remarkable success in recent years. However, not all patients respond to immunotherapy, highlighting the need to understand the factors that influence its effectiveness. One critical aspect is the tumor microenvironment (TME), the complex ecosystem surrounding the tumor that can either promote or suppress immune responses.

Within the TME, host metabolism—the way the body processes nutrients and energy—plays a significant role. Chronic inflammation, often fueled by metabolic imbalances, can hinder the immune system's ability to recognize and attack cancer cells. As combined approaches involving immunotherapy and radiation therapy (RT) become increasingly common, researchers are exploring ways to manipulate host metabolism to enhance treatment outcomes.

Recent research presented at a major scientific conference sheds light on this fascinating intersection of metabolism, immunity, and radiation therapy. The study investigates how caloric restriction (CR), a dietary intervention that reduces calorie intake, can modulate the effects of radiation therapy and potentially prime the host for a better response to immunotherapy. This article delves into the key findings of this research, offering insights into the potential of metabolic interventions to revolutionize cancer treatment.

How Does Caloric Restriction Enhance Radiation Therapy's Impact on the Immune System?

Radiation beam intersecting metabolic pathways, activating immune cells.

The study, led by researchers at Sidney Kimmel Medical College at Thomas Jefferson University, explored the effects of combining radiation therapy with caloric restriction in a preclinical model of triple-negative breast cancer. Triple-negative breast cancer is an aggressive form of breast cancer that does not respond to hormonal therapies or targeted drugs, making it a particularly challenging disease to treat.

The researchers used a mouse model of triple-negative breast cancer to investigate the impact of caloric restriction on the tumor microenvironment. Mice were divided into four groups: those fed ad libitum (AL), those receiving radiation therapy (RT) alone, those undergoing caloric restriction (CR) alone, and those receiving both caloric restriction and radiation therapy (CR+RT). The primary tumor tissue was then analyzed to assess changes in immune markers.

STAT3 and STAT5: Radiation therapy alone increased STAT3 and STAT5, proteins that can suppress the immune system. Caloric restriction alone decreased these proteins, and this decrease was maintained when combined with radiation therapy.
miR-21: MiR-21, a molecule that promotes inflammation, was increased by radiation therapy but decreased by both caloric restriction and the combination of caloric restriction and radiation therapy.
T Cell Function: Radiation therapy decreased the levels of IFNg, a cytokine that promotes T cell activity, but caloric restriction increased IFNg levels. Conversely, radiation therapy increased IL-10, an immunosuppressive cytokine, but caloric restriction decreased IL-10 levels.

To validate these preclinical findings, the researchers also conducted a feasibility trial in early-stage breast cancer patients undergoing radiation therapy. Patients were placed on a diet that reduced their caloric intake by 25% for 10 weeks concurrently with radiation therapy. Serum samples were collected before and after treatment to measure changes in cytokine levels and microRNA expression. The results mirrored the preclinical findings, with increased memory T cell cytokines and decreased Treg cytokines observed in patients undergoing caloric restriction in combination with radiation therapy.

The Future of Cancer Treatment: Combining Metabolism and Immunity

This research highlights the potential of targeting host metabolism to enhance the effectiveness of cancer treatments. By combining caloric restriction with radiation therapy, researchers were able to modulate the tumor microenvironment, reduce immunosuppression, and promote a more favorable immune response. These findings suggest that dietary interventions, such as caloric restriction, may play a crucial role in optimizing cancer treatment outcomes, particularly in combination with immunotherapy.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1016/j.ijrobp.2018.06.128, Alternate LINK

Title: Harnessing Metabolism With Radiation Therapy To Modulate Host Immunity In The Tumor Microenvironment

Subject: Cancer Research

Journal: International Journal of Radiation Oncology*Biology*Physics

Publisher: Elsevier BV

Authors: B. Simone, G. Manukian, K. Ko, T. Deangelis, S. Bhattacharya, A. Berger, N.L. Simone

Published: 2018-11-01

Everything You Need To Know

What is the tumor microenvironment and why is it important?

The tumor microenvironment (TME) is the ecosystem surrounding a tumor, significantly influencing immune responses. Its importance lies in its ability to either promote or suppress the immune system's ability to fight cancer. A TME that suppresses immune responses can hinder immunotherapies, making it crucial to understand and modulate the TME to improve cancer treatment outcomes. Factors such as chronic inflammation and metabolic imbalances play a significant role within the TME and directly affect the immune system's ability to recognize and attack cancer cells.

What is caloric restriction and why is it relevant to cancer treatment?

Caloric restriction (CR) is a dietary intervention that reduces calorie intake. CR is important because research suggests it can modulate the effects of radiation therapy (RT) and potentially improve a patient's response to immunotherapy. Implications include the possibility of enhancing cancer treatment outcomes through dietary changes by manipulating host metabolism to create a more favorable environment for the immune system to attack the tumor. In some trials, patients reduced their caloric intake by 25% for 10 weeks concurrently with radiation therapy to measure the effects.

What is radiation therapy and how does it affect the immune system in cancer treatment?

Radiation therapy (RT) is a cancer treatment that uses high doses of radiation to kill cancer cells and shrink tumors. Its significance, in the context of modulating the immune system, lies in its interaction with host metabolism and its potential to either suppress or enhance immune responses depending on the conditions within the tumor microenvironment (TME). Research indicates that combining RT with caloric restriction (CR) can alter the TME in ways that reduce immunosuppression and promote a more favorable immune response, making RT more effective when combined with specific dietary interventions.

What are STAT3 and STAT5, and what role do they play in the body's response to radiation therapy and caloric restriction?

STAT3 and STAT5 are proteins that can suppress the immune system. They are significant because radiation therapy (RT) alone can increase their levels, potentially hindering the body's ability to fight cancer. Caloric restriction (CR) has been shown to decrease these proteins, and this decrease is maintained even when combined with radiation therapy. This implies that incorporating CR with RT could counteract the immunosuppressive effects of RT, leading to improved cancer treatment outcomes by allowing the immune system to function more effectively.

What is miR-21, and how does it relate to cancer treatment and the interaction between radiation therapy and caloric restriction?

MiR-21 is a molecule that promotes inflammation. It is important in the context of cancer because radiation therapy (RT) can increase miR-21 levels, contributing to inflammation in the tumor microenvironment (TME), which can suppress the immune response. Caloric restriction (CR), however, can decrease miR-21 levels. Implications include that by combining CR with RT, the reduction in miR-21 can help reduce inflammation, potentially creating a more favorable environment for the immune system to attack cancer cells.