HIF1A and neoplasm: GPR132, a proton-sensing GPCR expressed by macrophages, mediates chemotaxis toward acidic, lactate-rich microenvironments enriched in dying cells by sensing lactate-induced acidification; this activates the MyD88–PI3K–AKT–MMP9 signaling axis and not only facilitates clearance of necrotic debris but also reprograms macrophages toward an M2-like tumor-promoting phenotype, characterized by increased motility, phagocytosis, and expression of metabolic genes (e.g., Hif1α, Ldha) and immunoregulatory markers [52,56].