Cancer-generated lactic acid: a regulatory, immunosuppressive metabolite?
Stephen Yiu Chuen Choi,Colin Collins,Colin Collins,Peter W. Gout,Yuzhuo Wang,Yuzhuo Wang,Yuzhuo Wang +6 more
Reads0
Chats0
TLDR
It is proposed 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.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. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.read more
Citations
More filters
Journal ArticleDOI
Emerging applications of metabolomics in drug discovery and precision medicine
TL;DR: This Review discusses some of the latest technological advances in metabolomics, focusing on the application of metabolomics towards uncovering the underlying causes of complex diseases, the growing role of metabolites in drug discovery and its potential effect on precision medicine.
Journal ArticleDOI
T Cell Dysfunction in Cancer.
TL;DR: The current understanding of T cell dysfunction in cancer, the value of novel technologies to dissect such dysfunction at the single cell level, and how the emerging understanding may be utilized to develop personalized strategies to restore antitumor immunity are discussed.
Journal ArticleDOI
Metabolic Interactions in the Tumor Microenvironment
TL;DR: The focus of this review is on the remodeling of the tumor microenvironment that leads to pathophysiologic interactions that are influenced and shaped by metabolism.
Journal ArticleDOI
Regulation of pyruvate metabolism and human disease.
TL;DR: Because most major diseases involve aberrant metabolism, understanding and exploiting pyruvate carbon flux may yield novel treatments that enhance human health.
Journal ArticleDOI
Comprehensive review on lactate metabolism in human health.
María M. Adeva-Andany,M. López-Ojén,R. Funcasta-Calderón,E. Ameneiros-Rodríguez,C. Donapetry-García,M. Vila-Altesor,J. Rodríguez-Seijas +6 more
TL;DR: Available evidence suggests an association between defective mitochondrial oxidative capacity in the pancreatic β-cells and diminished insulin secretion that may trigger the development of diabetes in patients already affected with insulin resistance, although the pathogenesis remains unsettled.
References
More filters
Journal ArticleDOI
Hallmarks of cancer: the next generation.
TL;DR: Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.
Journal ArticleDOI
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
TL;DR: It is proposed that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass needed to produce a new cell.
Journal ArticleDOI
Why do cancers have high aerobic glycolysis
TL;DR: In this article, the authors propose that persistent metabolism of glucose to lactate even in aerobic conditions is an adaptation to intermittent hypoxia in pre-malignant lesions, which leads to microenvironmental acidosis requiring evolution to phenotypes resistant to acid-induced cell toxicity.