Lactic acid, a driver of tumor-stroma interactions

•Lactic acid induces metabolic reprogramming enable fibroblasts, macrophages, adipocytes and vascular endothelial cells to survive and thrive in tumor microenvironment where is nutrient deprivation and acidosis.•Lactic acid contributes to transformation of fibroblasts, macrophages, adipocytes and vascular endothelial cells, which converts them from bystander or anti-tumor agents to carcinogenic agents.•MCT1, LDHB, GPR81, GPR132, and ASICs may be the key regulators of lactic acid mediated tumor-stroma interaction. Warburg effect is one of the hallmarks of tumor favoring the suppression of normal oxidative phosphorylation (OxPhos) and the adaptation to hypoxia. In addition to providing continuous energy to meet the demands of tumors, acceleratedWarburg effect also producesa large amount of lactic acid. Lactic acid shuttles between different cell populations within the tumor microenvironment (TME) and confers tumor cells to interact with surrounding cells, which has emerged as a new phenomenon in the field of tumor biology and tumorigenesis. Lactic acid not only fulfills the energetic demands of stromal cells, but becomes a major regulator of their activity by serving as a signaling molecule. Activated stromal cells in turn support tumor development. In this review, we discuss the role of lactic acid in transformation and oncogenic function of stromal cells including fibroblasts, macrophages, adipocytes and vascular endothelial cells, and suggest the relevance of lactic acid in therapy response and essential questions in this field.