Chinese researchers have found that caloric restriction may inhibit tumor growth by affecting how tumors send signals.

The findings, which could enhance existing cancer treatments, were published last month in the journal Cancer Research in a joint study by researchers at Sun Yat-sen University Cancer Center, Guangdong Provincial People’s Hospital, the Cancer Hospital of Shantou University Medical College, and St. John’s University in New York City. 

Observing how caloric restriction impacts tumor size and number in mice with breast tumors, the researchers found that caloric restriction disrupts the signals tumors use to recruit and reprogram the body’s wound-healing cells — known as cancer-associated fibroblasts (CAFs) — for their own use. This helps to convert the tumor’s immunosuppressive environment into one more favorable to cancer-fighting cells.

Yang Lu, the study’s corresponding author and a doctor at Guangdong Provincial People’s Hospital, told Sixth Tone that the idea for the study arose from questions about diet that she and the other researchers frequently receive from patients. 

“Patients are always asking us, ‘What should I eat? How should I eat?’” Yang said. “To be honest, I didn’t know how to answer that before. But I really wanted to find a clear answer to that question.”

The study used a dietary program on the mice known as a “fasting-mimicking diet,” or FMD, in which calorie intake is sharply reduced, triggering a series of stress responses and cellular repair functions. 

Research in recent years has shown that an FMD may enhance anti-cancer immunity in several instances, including altering gut microbiota to suppress colorectal cancer and enhancing breast cancer endocrine therapy. However, exactly how the method works and how it might inform cancer treatment remains unclear.

Previous research has predominantly focused on how FMDs alter tumor cells, tumor-attacking T cells, and the environment of cells, molecules, and blood vessels in the presence of tumors. This latest study instead examined the diet’s effects on CAFs.

The researchers randomly divided the mice into two groups: mice with unrestricted access to food and mice that underwent FMD — a cycle of one day of 50% calorie restriction, three days of 90% calorie restriction, and three days of unrestricted feeding. The experiment lasted three weeks.

The results showed that tumors in mice on a calorie-restricted diet were significantly reduced in volume and weight. The number of spontaneously occurring tumors in the diet group also significantly decreased.

Through RNA sequencing and cell-cell communication analysis, the researchers found less glucose availability and tumor-cell breakdown in the dieting mice. This in turn lowered secretion of the signaling molecule PDGFC, a CAF-binding protein released by tumor cells to suppress the host’s immune system. 

This also reduced the proportion of immunosuppressive, inflammatory CAFs (iCAFs), while increasing the proportion of tumor cells with signs of programmed cell death. As a result, the tumor’s immunosuppressive environment was weakened, allowing more immune system cells to enter and fight the tumor.

The team also found that combining caloric restriction with a PDGFR inhibitor, a drug used to block tumor blood vessel formation, further weakened the tumor’s immunosuppressive environment. The results suggest that such a diet could work alongside existing cancer therapies to enhance anti-tumor activity.

However, the researchers noted several limitations. Among them, the study did not examine in detail how iCAFs affect the behavior and function of immune cells within tumors. It also remains unclear how the study’s mechanisms may impact different tumor types. 

The authors wrote that while fasting “holds promise” as a way to enhance or work alongside cancer treatment, “large-scale clinical trials are needed to validate its efficacy, safety, and feasibility in cancer patients, alongside biomarker studies to optimize … combination therapy and long-term outcomes.”

Yang, the corresponding author, said the team has already begun incorporating FMD-based dietary recommendations into clinical trials involving cancer patients. Patients may be advised to reduce their calorie intake for several days before and after a treatment cycle, although specific dietary plans may vary.

In the future, the team hopes to develop better drugs and dietary interventions and eventually extend the approach to other cancer types.

“People’s lifestyles and individual differences are very diverse,” Yang said. “As the research becomes clearer, we hope to eventually develop personalized nutrition plans for different patients.”

Editor: Marianne Gunnarsson.

(Header image: Science Photo library/VCG)