Creatine in T Cell Antitumor Immunity and Cancer Immunotherapy

Creatine is a broadly used dietary supplement that has been extensively studied for its benefit on the musculoskeletal system. Yet, there is limited knowledge regarding the metabolic regulation of creatine in cells beyond the muscle. New insights concerning various regulatory functions for creatine in other physiological systems are developing. Here, we highlight the latest advances in understanding creatine regulation of T cell antitumor immunity, a topic that has previously gained little attention in the creatine research field. Creatine has been identified as an important metabolic regulator conserving bioenergy to power CD8 T cell antitumor reactivity in a tumor microenvironment; creatine supplementation has been shown to enhance antitumor T cell immunity in multiple preclinical mouse tumor models and, importantly, to synergize with other cancer immunotherapy modalities, such as the PD-1/PD-L1 blockade therapy, to improve antitumor efficacy. The potential application of creatine supplementation for cancer immunotherapy and the relevant considerations are discussed.

Automated summary

Creatine is widely used as a dietary supplement with known benefits on the musculoskeletal system, but its metabolic regulation beyond muscle cells is not well understood. Recent research highlights the diverse regulatory functions of creatine in various physiological systems, especially its role in enhancing T cell antitumor immunity. Creatine supplementation has been shown to boost antitumor T cell immunity and synergize with other cancer immunotherapy modalities to improve antitumor efficacy.