title: Tumor cells and memory T cells converge at glycolysis: therapeutic implications.
abstract: In the immune system, activation of naïve T (Tn) cells into effector T cells (Teff) involves a metabolic switch to glycolysis 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 (Tems) cells glycolytic phenotype contributes to the shortened lifespan of Tems. Conversely, inhibition of glycolysis in Tems not only extended their viability but also augmented desirable properties. Notably, they also demonstrate 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 metabolic reprogramming which involves a shift toward glycolysis (the conversion of glucose into lactate) to facilitate uninterrupted growth. Interestingly, antiglycolytic treatment of cancer cells has been known to trigger antitumor immune response as well. Taken together, it is probable that a strategy involving concurrent inhibition of glycolysis in tumor cells and Tems could promote a dual attack on cancer by inducing an effective antitumor immune response and an immunogenic chemotherapy.
authors.affiliation: Department of Radiology & Radiological Sciences; Johns Hopkins University School of Medicine; Baltimore, MD USA.
authors.forename: Swathi
authors.initials: S
authors.lastname: Karthikeyan
authors.affiliation: Department of Radiology & Radiological Sciences; Johns Hopkins University School of Medicine; Baltimore, MD USA.
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Geschwind
authors.affiliation: Department of Radiology & Radiological Sciences; Johns Hopkins University School of Medicine; Baltimore, MD USA.
authors.forename: Shanmugasundaram
authors.initials: S
authors.lastname: Ganapathy-Kanniappan
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects*; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D008546:Melanoma, Experimental / Q000276:immunology*
keywords: T cells; cancer; chemotherapy; glycolysis; immunotherapy