Zinc mediates the interplay between Th1/Treg differentiation and regulates anti-tumor immunity

Abstract Dietary supplements play an important role in determining the health and immunity. Zn supplement has been used for the dietary chemoprevention of cancer. However, some of the studies say that Zn is important for cell proliferation and cells in the Zn deficient condition arrested in the S-phase of cell cycle. Dietary Zn deficiency is known to inhibit several types of animal tumors. Cancer cells have upregulated Zn importers and increased Zn levels and Zn deficiency induces cell death via apoptosis. As Zn supplementation is widely used a detailed study analysing the effects of Zn on tumor progression has become the necessity of this hour. In this study we have identified that providing higher doses of Zn supplement for longer duration during tumor development results in increased tumor burden. Zn supplementation during tumor development alters mainly CD4 T cell subtypes by suppressing T helper 1 (Th1) cell population and enhancing T regulatory (Treg) cell population. Zn supplementation significantly increases PD1 immune checkpoints on CD4 T cells, CD8 T cells and γδT cells. The degranulation marker CD107a or LAMP1 expression on NK cells and CD8 T cells decreased indicating the decrease in cytotoxicity among these cells by Zn supplementation. Our findings open excellent therapeutic avenues for targeting cancer. Firstly use of Zn chelators as a tumor therapeutic agent. Zn chelators can be combined with α-PD1 mAb checkpoint therapy to overcome the drawbacks of immune checkpoint therapy and efficient treatment outcome. Secondly trace element analysis can become the forefront of cancer immunotherapy, as our study along with many other reports prove that the level of trace elements determines the tumor development and therapeutic outcome. Supported by grants from Department of Bio-Technology (DBT), Ministry of Science and Technology, Govt. of India.