2. Academic Validation
  3. Dysfunction of Natural Killer Cells by FBP1-Induced Inhibition of Glycolysis during Lung Cancer Progression

Dysfunction of Natural Killer Cells by FBP1-Induced Inhibition of Glycolysis during Lung Cancer Progression

  • Cell Metab. 2018 Aug 7;28(2):243-255.e5. doi: 10.1016/j.cmet.2018.06.021.
Jingjing Cong 1,  Xianwei Wang 1,  Xiaohu Zheng 1,  Dong Wang 1,  Binqing Fu 2,  Rui Sun 2,  Zhigang Tian 3,  Haiming Wei 4
Affiliations

Affiliations

  • 1 The CAS Key Laboratory of Innate Immunity and Chronic Disease and Institute of Immunology, School of Life Science and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China.
  • 2 The CAS Key Laboratory of Innate Immunity and Chronic Disease and Institute of Immunology, School of Life Science and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China; Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, Anhui 230027, China.
  • 3 The CAS Key Laboratory of Innate Immunity and Chronic Disease and Institute of Immunology, School of Life Science and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China; Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, Anhui 230027, China. Electronic address: tzg@ustc.edu.cn.
  • 4 The CAS Key Laboratory of Innate Immunity and Chronic Disease and Institute of Immunology, School of Life Science and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China; Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, Anhui 230027, China. Electronic address: ustcwhm@ustc.edu.cn.
PMID: 30033198 DOI: 10.1016/j.cmet.2018.06.021
Abstract

Natural killer (NK) cells are effector lymphocytes with pivotal roles in the resistance against various tumors; dysfunction of NK cells often results in advanced tumor progression. Tumors develop in three stages comprising initiation, promotion, and progression, but little is known about the interrelationships between NK cells and tumor cells at different stages of tumor development. Here, we demonstrated that NK cells prevented tumor initiation potently but did not prevent tumor promotion or tumor progression in Kras-driven lung Cancer. Moreover, loss of the antitumor effect in NK cells was closely associated with their dysfunctional state during tumor promotion and progression. Mechanistically, aberrant fructose-1,6-bisphosphatase (FBP1) expression in NK cells elicited their dysfunction by inhibiting glycolysis and impairing viability. Thus, our results show dynamic alterations of NK cells during tumor development and uncover a novel mechanism involved in NK cell dysfunction, suggesting potential directions for NK cell-based Cancer Immunotherapy involving FBP1 targeting.

Keywords

FBP1; NK cell dysfunction; glycolysis; lung cancer.

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