Effects of high-intensity aerobic exercise training on tumor-specific immune and inflammatory response in NSCLC patients

• Applicant: Dr. Katharina Leuchte
• Subject Area: Hematology, Oncology ; Anatomy and Physiology ; Immunology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 505368854

Cells of the immune system, specifically NK and T cells can recognize and kill cancer cells while leaving normal cells untouched. Over the past few years, this capacity has been successfully exploited to develop immunotherapies against cancer. Even some previously very hard-to-treat cancers - e.g., lung cancer - are now successfully treated with immunotherapy. However, not all patients benefit from treatment. In some cancer nodules, NK and T cells are present in large numbers, and patients harboring such tumors are more prone to benefit from treatment. Thus, ways by which T cell migration to the tumor could be improved may lead to a better chance for response to immunotherapy, and thus better survival and maybe even cure from disease. Exercise is known to mobilize cells of the immune system, in particular T and NK cells, and results from mouse tumor studies have demonstrated that exercising animals harbor tumors with brisk infiltration of immune cells, and these animals live longer and respond better to immunotherapy. Accordingly, exercise could represent an ideal combination partner to immunotherapy. This concept is currently being tested in a clinical trial for patients with metastatic non-small cell lung cancer (NSCLC). The trial; “High Intensity Aerobic exercise training and Immune cell Mobilization in patients with lung cancer (HI-AIM; NCT04263467)”, will include 70 patients that all receive regular oncological treatment including immunotherapy. In addition, 35 patients (treatment arm) will conduct a monitored and supervised exercise program, and all 70 patients will form the basis for collection of biological samples; serum, blood, and tumor biopsy material. Here, we comprehensively analyze samples from healthy volunteers and patients – exercising as well as controls – for the impact of exercise on the immune system. We aim to study immune cell mobilization of various immune cell subsets, with an emphasis on previously activated cytotoxic T cells capable of recognizing virally infected cells as well as cancer cells. We hypothesize that exercise preferentially mobilizes this cell subset as well as NK cells, and we will study these cell types longitudinally for functionality, metabolism, and dynamics over treatment. Importantly, we will establish genetic fingerprints of the cells enabling tracking of exercise mobilized CD8+ T cells to tumor biopsy material. The proposed translational project will significantly expand functional understanding of the immune response to exercise therapy in NSCLC patients. This important and unique data may present the proof of principle of how exercise indeed aids improved response to immunotherapy in cancer patients. Consequently, this research project is of great importance for cancer patients and thus has significant social relevance.

• DFG Programme: WBP Fellowship
• International Connection: Denmark
• Host: Professor Dr. Per Thor Straten