Journal
JOURNAL OF PATHOLOGY
Volume 230, Issue 4, Pages 350-355Publisher
WILEY
DOI: 10.1002/path.4218
Keywords
Warburg effect; aerobic glycolysis; glutaminolysis; lactic acid; immune suppression; tumour micro-environment
Funding
- Canadian Institutes of Health Research
- BC Cancer Foundation
- Overseas Chinese Scholar Award from the National Natural Science Foundation of China
- International Cancer Alliance for Research and Education (ICARE)
- Tianjin Thousand Talents Program
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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. Copyright (c) 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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