LMP1-mediated glycolysis induces myeloid-derived suppressor cell expansion in nasopharyngeal carcinoma

Ting-Ting Cai, et al.

PLoS Pathog 13(7): e1006503

Speaker: Ming-Yu Shieh (謝明育)             Time: 13:00-14:00, Oct. 11, 2017

Commentator: Dr. Ai-Li Shiau (蕭璦莉老師)   Place: Room 601

Abstract:

        Epstein-Barr virus (EBV) is a DNA virus associated with a variety of cancers such as Burkitt’s lymphoma, Hodgkin’s lymphoma and nasopharyngeal carcinoma (NPC). Among EBV-encoded oncoproteins expressed in NPC, latent membrane protein 1 (LMP1) has been shown to induce glycolysis and immune escape, two events linked to cancer development [1-2]. Interestingly, metabolic reprogramming toward glycolysis promotes differentiation of CD33⁺ myeloid cells into myeloid-derived suppressor cells (MDSCs), which facilitate immune escape [3]. The authors of this study proposed that LMP1-induced immune escape may involve glycolysis-induced MDSCs. First, in agreement with previous studies, LMP1 induced many glycolysis-related genes, including the glucose transporter GLUT1, in NPC cells. LMP1 also induced a panel of MDSC-related factors, such as COX2, iNOS, ARG1, NLRP3, IL-1β, IL-6 and GM-CSF, and LMP1-expressing NPC cells promoted MDSC differentiation in a paracrine manner. Notably, inhibition of glycolysis by GLUT1 knockdown or 2-DG treatment reduced LMP1-induced expression of MDSC-related cytokines and paracrine-mediated MDSC differentiation, indicating that LMP1 promotes MDSC differentiation through glycolysis. Furthermore, NLRP3 knockdown in LMP1-expressing NPC cells reduced IL-1β production and MDSC differentiation, indicating that NLRP3 inflammasome-mediated IL-1β production is involved in LMP1-induced MDSC differentiation. In conclusion, this study reveals a critical link between metabolism and immune escape in EBV-associated NPC. Therefore, glycolysis-targeting pharmaceuticals may bring additional benefits to NPC therapy through counteracting immune suppression in the tumor microenvironment.

Reference:

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