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Background Normal cellular metabolism is altered in cancer cells, shifting away from the TCA cycle towards glycolysis, increasing glucose consumption and lactate production. This key characteristic change in metabolism is termed the Warburg effect. Importantly, HPV 16 E7 oncoprotein alters the function pyruvate kinase type M2, increasing glucose consumption and lactate production. Clinically, increased lactate production in head and neck cancers is associated with a decreased response to therapy. Cancers with high lactate production have a poor five year survival, approximately 40% worse than similar tumors with low lactate production. Lactate has also recently been shown to disrupt functions of key immune cells (CD8 and DC’s) in vitro. We have recently shown that an immune response is required to clear HPV+ head and neck squamous cell carcinomas (HNSCC) in vivo. In this project we tested the hypothesis that lactate within the tumor microenvironment inhibits immune mediated clearance of HPV+ cancers.

HPV+ cancer cell lactate production attenuates immune response during treatment: lactate production inhibition leads to improved long-term cures