Assessing the effects of lactate on the immune responsiveness of T cells in vitro

Abstract

T cells play a key role in protecting the body from cancer. While T cells are normally effective in destroying abnormal cells, there are times when malignancies grow seemingly unchecked by the immune system. Chimeric antigen receptor (CAR)-T cell therapy implements T cells that have been genetically engineered to recognize and kill cancer cells. While CAR-T cell therapy has demonstrated efficacy in treating hematological malignancies, it has shown less promise in treating solid tumors. A possible explanation for the decreased efficacy of T cells and T cell-based immunotherapies in destroying solid tumors may lie in a phenomenon that scientists have long been aware of. The Warburg effect, first described in 1924, is the observation that cancer cells tend to consume significantly more glucose than other cells due to their shift from aerobic respiration to fermentation, resulting in the accumulation of the waste product lactate in the tumor microenvironment. This research investigated the effects of lactate on the immune responsiveness of T cells, using Jurkat E6.1 cells and human primary T cells as models. The effects of lactate on viability, CD3 surface expression, and proliferation were assessed via flow cytometry. While lactate concentration and exposure time had no significant effects on T cell viability, marked decreases in CD3 surface expression and proliferation were observed following exposure to lactate. These findings may shed light on how solid tumors evade immune detection and immunotherapies and have implications for future approaches to treating solid tumors.