Tumor cells and memory T cells converge at glycolysis
Swathi Karthikeyan, Jeff Geschwind, and Shanmugasundaram Ganapathy-Kanniappan* Department of Radiology & Radiological Sciences; Johns Hopkins University School of Medicine; Baltimore, MD USA
In the immune system, activation of
naïve T (T ) cells into effector T cells n
(Teff) involves a metabolic switch to gly- colysis to promote rapid proliferation and differentiation. In the October issue of The Journal of Clinical Investigation, Sukumar et al. have demonstrated that in CD8+ memory T (T ) cells glycolytic
lifespan of Tems. Conversely, inhibition of glycolysis in Tems not only extended their viability but also augmented desirable properties. Notably, they also demon- strate that glycolytic inhibition during the ex vivo clonal expansion of tumor- specific Tems enhanced their antitumor function. Overall, the data suggest that an antiglycolytic strategy targeting the Tems could enhance antitumor immune response. On the other hand, cancer cells have long been known to exhibit meta- bolic reprogramming which involves a shift toward glycolysis (the conversion of glucose into lactate) to facilitate uninter- rupted growth. Interestingly, antiglyco- lytic treatment of cancer cells has been known to trigger antitumor immune response as well. Taken together, it is probable that a strategy involving con- current inhibition of glycolysis in tumor cells and Tems could promote a dual attack on cancer by inducing an effective anti- tumor immune response and an immu- nogenic chemotherapy.