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

乳酸是由糖酵解和氨解的终产物丙酮酸产生的代谢产物。它在肿瘤中含量丰富，因为肿瘤细胞通常表现出糖酵解活性升高和柠檬酸循环活性降低。乳酸盐可以被一些细胞用作催化剂和ATP生成的碳源，但乳酸似乎对效应T细胞具有拮抗作用。因此，预计乳酸会降低CAR T细胞在肿瘤中的效力。这将建立模型来剖析乳酸对CAR T细胞的拮抗作用，并评估抵消它们的策略。

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.