Recent research has revealed that elevated levels of lactate in the tumor microenvironment can impair the functionality of natural killer (NK) cells, a critical component of the body’s innate immune defense against cancer. The mechanism behind this dysfunction is attributed to lactate-induced lysine lactylation (Kla), a posttranslational modification that alters protein function within cells.
The study highlights how tumor-derived lactate accumulates in the microenvironment and leads to increased Kla on key proteins within NK cells. This biochemical alteration results in reduced cytotoxic activity, thereby diminishing the NK cells’ ability to identify and eliminate malignant cells.
NK cells are known for their ability to swiftly target and destroy tumor and virally infected cells without prior sensitization, making them pivotal in immunosurveillance. However, the hostile metabolic conditions created by cancer cells—including high concentrations of lactate due to aerobic glycolysis—can undermine this immune response.
This discovery opens potential therapeutic avenues for enhancing NK cell activity. One such strategy could involve limiting Kla or modifying NK cells genetically or pharmacologically to resist lactylation, thereby restoring or enhancing their cytotoxic function in cancer patients.
Future research will likely focus on the specific proteins affected by Kla in NK cells, and on developing agents that can mitigate or reverse these modifications. Such interventions could significantly boost the effectiveness of NK cell-based cancer immunotherapies by counteracting an immunosuppressive tumor microenvironment.
Source: https:// – Courtesy of the original publisher.
