Determining and combating the effects of lactic acid on CAR T cells

乳酸是糖酵解和谷氨酰胺分解的最终产物丙酮酸产生的代谢物。它在肿瘤中大量存在，因为肿瘤细胞典型地表现出糖酵解活性升高和柠檬酸循环活性降低。乳酸可以被一些细胞用作分解代谢和生成ATP的碳源，但乳酸似乎对效应性T细胞具有拮抗作用。因此，乳酸预计会降低肿瘤中CAR T细胞的效力。这将建立模型来剖析乳酸对CAR T细胞的拮抗作用，并评估对抗它们的策略。

Lactic acid is a metabolite generated from pyruvate the end-product of glycolysis and glutaminolysis. It is abundant in tumours, as tumour cells typically demonstrate elevated glycolytic activity and decreased citric acid cycle activity. Lactate can be utilised by some cells as a carbon source for catabolism and ATP generation but lactic acid appears to be antagonistic to effector T cells. Lactic acid is therefore anticipated to diminish the potency of CAR T cells in tumours. This will establish models to dissect the antagonistic effects of lactic acid on CAR T cells and to evaluate strategies to counteract them.