Targeted nutritional strategies and structured physical activity can modulate immune function, offering promising complementary approaches to enhance immune competence in vulnerable populations, such as older adults and patients with cancer.

Integrating these interventions early into care pathways is clinically relevant because emerging evidence suggests that the strength of the immune system is modifiable rather than inevitable in ageing and cancer. Two researchers detailed the underlying biological mechanisms during the French Nutrition Days 2025, held from 10 to 12 December in Lyon, France.

Presentations highlighted how malnutrition, muscle loss, and sedentary behaviour accelerate immune dysfunction, whereas dietary interventions and physical activity may partially restore immune competence. Speakers have emphasised the clinical relevance of integrating these approaches early into the care pathways for ageing populations and individuals undergoing cancer treatment.

Immunosenescence Mechanisms

Ageing is associated with a decrease in muscle mass, known as sarcopenia, and an increase in fat mass. These changes are partly driven by malnutrition that is prevalent in individuals older than 65 years. The prevalence ranges from 4% to 10% among those living at home, 15% to 35% among those in institutions, and up to 30% to 70% among hospitalised patients.

Malnutrition is often linked to reduced appetite caused by altered taste and smell, difficulty adapting, and modification of dietary intake. This creates what Delphine Sauce, PhD, researcher at the Centre for Immunology and Microbial Infections, Paris, France, described as a “vicious circle.”

Malnutrition leads to the loss of muscle mass and a weakened immune system, increasing the risk for infection. Paradoxically, infectious episodes require a higher caloric intake, further worsening nutritional status.

Malnutrition carries a major prognostic burden, with the risk for morbidity increasing four- to sixfold and the risk for mortality increasing four- to eightfold compared to age-matched individuals who are not malnourished.

From a biological standpoint, immunosenescence represents a functional immune decline driven by reduced production of haematopoietic stem cells in the bone marrow, which becomes increasingly fatty. The differentiation of these cells shifts towards the myeloid compartment rather than the adaptive lymphoid compartment.

At the innate immunity level, a qualitative defect was observed. Natural killer cells and macrophages remain present in sufficient numbers but show reduced responsiveness, including diminished stress responses, impaired antigen presentation, and reduced mobilisation.

Both quantitative and qualitative declines in T and B lymphocytes have been observed in adaptive immunity. Thymic involution and reduced bone marrow function impair immune cooperation and adaptive responses.

In parallel, older adults develop chronic low-grade inflammation, known as inflammaging. This process is linked to ageing and is promoted by increased intestinal permeability and microbial translocation across the gut barrier.

Several nutritional strategies have been evaluated to counteract these mechanisms. These include:

• Strengthening the intestinal barrier through prebiotics, probiotics, postbiotics, or synbiotics
• Targeted supplementation with minerals and vitamins to support immune function
• Pharmacologic and nutraceutical anti-ageing approaches

Many studies have focused on agents that target senescent cells that accumulate with age and produce a secretome that is harmful to the immune system. These approaches include senolytics, which induce the lysis of senescent cells, and senomorphics, which regulate senescent cell activity. Examples of senomorphics include rapamycin, metformin, and resveratrol.

Exercise and Immunity

Physical activity may also modulate immune function, as suggested by multiple studies. Research has shown increased peripheral mobilisation of CD8+ T lymphocytes and natural killer cells following exercise. One hour after physical exertion, natural killer cell cytotoxic immune capacity against certain cancer cell lines reportedly increased by approximately 60%.

These effects appear to be mediated largely by improved blood perfusion, which enhances tumour infiltration by immune cells, treatments, oxygen, and nutrients. Improved tumour perfusion is a key strategy for reducing hypoxia-induced immune resistance and enhancing the effectiveness of cancer therapies.

Preclinical studies in murine cancer models have shown that physical activity increases the sensitivity of cancer cells to immune checkpoint inhibitors. Tumour reduction was greater than in mice receiving only the treatment or physical activity alone.

These findings informed the ERICA trial conducted at the Centre Léon Bérard, Lyon, which involved patients with lung cancer who received immunochemotherapy. Manon Gouez, a PhD researcher in physical activity at the Department of Cancer Prevention and Environment at the Centre Léon Bérard, reviewed the results.

The study confirmed that supervised physical activity was feasible for most participants despite metastatic disease. The protocol included a cycling session immediately before each treatment cycle and a recommendation of 6000 steps per day, monitored using an actimeter.

Overall, 81% of patients were able to follow the protocol. The participants maintained a satisfactory level of physical activity and experienced improvements in their quality of life and sleep. Changes in immune cell proportions were modest. According to the investigators, “it is possible that the moderate intensity of exercise and the timing between exercise and treatment administration were insufficient.”

A larger clinical trial, ERICA 02, will integrate coached exercise sessions at home and during treatment to assess whether pronounced biological changes can be achieved.

Nevertheless, the integration of adapted physical activity is increasingly viewed as essential for supporting patients and improving their quality of life. Experts emphasised that physical activity should be discussed at the time of diagnosis to embed it early in the care pathway.

Achieving a certain level of activity and intensity appears necessary to maximise anti-tumour effects, supporting the need for professional supervision by trained adapted physical activity specialists. Across studies, physical activity has consistently been associated with improved sleep and quality of life.

This story was translated from Univadis France, part of the Medscape Professional Network.