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J Pathol. 2013 Aug;230(4):350-5. doi: 10.1002/path.4218.

Cancer-generated lactic acid: a regulatory, immunosuppressive metabolite?

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Department of Experimental Therapeutics, BC Cancer Agency, Vancouver, British Columbia, Canada.


The common preference of cancers for lactic acid-generating metabolic energy pathways has led to proposals that their reprogrammed metabolism confers growth advantages such as decreased susceptibility to hypoxic stress. Recent observations, however, suggest that it generates a novel way for cancer survival. There is increasing evidence that cancers can escape immune destruction by suppressing the anti-cancer immune response through maintaining a relatively low pH in their micro-environment. Tumours achieve this by regulating lactic acid secretion via modification of glucose/glutamine metabolisms. We propose that the maintenance by cancers of a relatively low pH in their micro-environment, via regulation of their lactic acid secretion through selective modification of their energy metabolism, is another major mechanism by which cancers can suppress the anti-cancer immune response. Cancer-generated lactic acid could thus be viewed as a critical, immunosuppressive metabolite in the tumour micro-environment rather than a 'waste product'. This paradigm shift can have major impact on therapeutic strategy development.


Warburg effect; aerobic glycolysis; glutaminolysis; immune suppression; lactic acid; tumour micro-environment

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