Potential functions of TRPM2 and TRPM7 channels in the tumor microenvironment

The tumor microenvironment (TME) is a complex and dynamic ecosystem consisting of both cellular and non-cellular components that collectively modulate the antitumor immune response, as well as cancer growth, invasion, metastasis, immune evasion, and resistance to therapy. Calcium (Ca2+) and magnesium (Mg2+) are two essential ions for a wide range of cellular processes, including proliferation, differentiation, migration, and protein secretion. The intracellular homeostasis and spatiotemporal distribution of these two ions are tightly regulated by ion channels, notably members of the transient receptor potential melastatin (TRPM) subfamily, such as TRPM2 and TRPM7. TRPM2 is a Ca2+-permeable channel activated by ADP-ribose (ADPR) and reactive oxygen species (ROS), whereas TRPM7 permeates both Ca2+ and Mg2+ ions and exhibits constitutive activity. Both channels have been involved in redox-sensitive signaling and function as temperature sensors across various physiological and pathological contexts, such as cancer. Here, we provide an overview of the potential roles of TRPM2 and TRPM7 in regulating cellular dynamics within the TME, with a focus on their contributions to immune modulation.