title: Cancer-generated lactic acid: a regulatory, immunosuppressive metabolite?
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.
authors.affiliation: Department of Experimental Therapeutics, BC Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Stephen Yiu Chuen
authors.initials: SY
authors.lastname: Choi
authors.forename: Colin C
authors.initials: CC
authors.lastname: Collins
authors.forename: Peter W
authors.initials: PW
authors.lastname: Gout
authors.forename: Yuzhuo
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002470:Cell Survival; D015195:Drug Design; D004734:Energy Metabolism / Q000187:drug effects; D006019:Glycolysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000378:metabolism*; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D019139:Tumor Escape / Q000187:drug effects; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D019344:Lactic Acid
keywords: Warburg effect; aerobic glycolysis; glutaminolysis; immune suppression; lactic acid; tumour micro-environment