Lactate, being an end product of glycolysis, is often considered to be a waste product. However, research over the past decades has shown its role as a critical energy source for mitochondrial respiration, lactate also acts as a precursor of gluconeogenesis and a signaling molecule.
Intracellular metabolism exerts some element of control over the functionality of immune cells, with high glycolytic rates observed during pro-inflammatory responses. Intracellular metabolism in inflammatory immune cells, resulting in high amounts of lactate production and secretion. Evidence suggests that lactate can induce reprogramming of immune cells towards cellular plasticity, which contributes to the establishment of disease-specific immunity status. For example, monocyte and macrophage phenotypes have been shown to exhibit plasticity in tumor microenvironments with high levels of lactate concentration, shifting towards a reduction in cytokine production. However, lactate-mediate reprogramming of immune cells not only has implications in cancer but also in the pathogenesis of autoimmune and autoinflammatory disorders and infections. However, further research is required to understand the specific mechanisms underlying the relationship between lactate concentration and immune cell plasticity.
Lactate secretion is also thought to be a major determinant of acidic extracellular pH, which is associated with tumor metastasis. An acidic tumor environment results in the expression of pro-metastatic factors and activates lysosomal enzymes. Antitumor immune responses have also been found to be initiated by a reduction in the acidity of the tumor microenvironment, which suggests its potential for therapeutic targeting.
In this Research Topic, we aim to highlight our current understanding of the immunomodulatory role of lactate in regulating inflammatory immune responses in various diseases and disorders. We will also welcome manuscripts focusing on novel molecular mechanisms underlying lactate-mediated reprogramming of immune cell plasticity towards inflammatory phenotypes in various pathologies. We welcome submissions focusing on the therapeutics exploiting lactate-mediated immunomodulation as a treatment of cancer, autoimmune and autoinflammatory disorders, and infectious diseases. Finally, we will also welcome manuscripts discussing lactate-mediated acidosis of the tumor microenvironment and related therapeutic targeting.
In this Research Topic, we welcome the submission of Original Research, Review, and Mini Review articles focusing on lactate metabolism and regulation of the immune response. We welcome submissions covering, but not limited to, the following sub-topics:
• Reviews of our current understanding of lactate-mediated modulation of immune cell plasticity
• Novel molecular mechanisms underlying lactate-mediated modulation of immune cell phenotypes
• The role of lactate-mediated immunomodulation in the pathogenesis of cancer, autoimmune and autoinflammatory diseases, and infectious diseases
• The role of lactate in regulating the acidity of the tumor immune microenvironment
• Therapeutics targeting lactate-mediated immunomodulation in the treatment of various inflammatory pathologies
• Therapeutic targeting of lactate-mediated tumor acidity in regulating antitumor immune
Lactate, being an end product of glycolysis, is often considered to be a waste product. However, research over the past decades has shown its role as a critical energy source for mitochondrial respiration, lactate also acts as a precursor of gluconeogenesis and a signaling molecule.
Intracellular metabolism exerts some element of control over the functionality of immune cells, with high glycolytic rates observed during pro-inflammatory responses. Intracellular metabolism in inflammatory immune cells, resulting in high amounts of lactate production and secretion. Evidence suggests that lactate can induce reprogramming of immune cells towards cellular plasticity, which contributes to the establishment of disease-specific immunity status. For example, monocyte and macrophage phenotypes have been shown to exhibit plasticity in tumor microenvironments with high levels of lactate concentration, shifting towards a reduction in cytokine production. However, lactate-mediate reprogramming of immune cells not only has implications in cancer but also in the pathogenesis of autoimmune and autoinflammatory disorders and infections. However, further research is required to understand the specific mechanisms underlying the relationship between lactate concentration and immune cell plasticity.
Lactate secretion is also thought to be a major determinant of acidic extracellular pH, which is associated with tumor metastasis. An acidic tumor environment results in the expression of pro-metastatic factors and activates lysosomal enzymes. Antitumor immune responses have also been found to be initiated by a reduction in the acidity of the tumor microenvironment, which suggests its potential for therapeutic targeting.
In this Research Topic, we aim to highlight our current understanding of the immunomodulatory role of lactate in regulating inflammatory immune responses in various diseases and disorders. We will also welcome manuscripts focusing on novel molecular mechanisms underlying lactate-mediated reprogramming of immune cell plasticity towards inflammatory phenotypes in various pathologies. We welcome submissions focusing on the therapeutics exploiting lactate-mediated immunomodulation as a treatment of cancer, autoimmune and autoinflammatory disorders, and infectious diseases. Finally, we will also welcome manuscripts discussing lactate-mediated acidosis of the tumor microenvironment and related therapeutic targeting.
In this Research Topic, we welcome the submission of Original Research, Review, and Mini Review articles focusing on lactate metabolism and regulation of the immune response. We welcome submissions covering, but not limited to, the following sub-topics:
• Reviews of our current understanding of lactate-mediated modulation of immune cell plasticity
• Novel molecular mechanisms underlying lactate-mediated modulation of immune cell phenotypes
• The role of lactate-mediated immunomodulation in the pathogenesis of cancer, autoimmune and autoinflammatory diseases, and infectious diseases
• The role of lactate in regulating the acidity of the tumor immune microenvironment
• Therapeutics targeting lactate-mediated immunomodulation in the treatment of various inflammatory pathologies
• Therapeutic targeting of lactate-mediated tumor acidity in regulating antitumor immune