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

The Journal of pathology (2013-06-05)
Stephen Yiu Chuen Choi, Colin C Collins, Peter W Gout, Yuzhuo Wang
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Lactic acid solution, ACS reagent, ≥85%
Sigma-Aldrich
DL-Lactic acid, ~90% (T)
Sigma-Aldrich
Lactic acid, 85%, FCC
Sigma-Aldrich
Lactic acid, meets USP testing specifications
Sigma-Aldrich
Lactic acid, natural, ≥85%
Supelco
Lactic acid, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
DL-Lactic acid, 85 % (w/w), syrup
USP
Lactic acid, United States Pharmacopeia (USP) Reference Standard