The consequent lactate overproduction serves dual tumor-promoting roles: extracellular acidification (pH 6.0-6.5) inhibits the cytotoxic activity of tumor-infiltrating lymphocytes and NK cells by impairing perforin/granzyme function, while lactate itself acts as a signaling molecule that induces VEGF secretion to stimulate angiogenesis [60, 61]. This evidence concerns the gene PRF1 and neoplasm.