PMID- 27995420
OWN - NLM
STAT- MEDLINE
DCOM- 20170718
LR  - 20220318
IS  - 1869-1889 (Electronic)
IS  - 1674-7305 (Linking)
VI  - 59
IP  - 12
DP  - 2016 Dec
TI  - Lactic acid in tumor microenvironments causes dysfunction of NKT cells by 
      interfering with mTOR signaling.
PG  - 1290-1296
AB  - Cellular metabolism has been shown to regulate differentiation and function of 
      immune cells. Tumor associated immune cells undergo phenotypic and functional 
      alterations due to the change of cellular metabolism in tumor microenvironments. 
      NKT cells are good candidates for immunotherapies against tumors and have been 
      used in several clinical trials. However, the influences of tumor 
      microenvironments on NKT cell functions remain unclear. In our studies, lactic 
      acid in tumor microenvironments inhibited IFNgamma and IL4 productions from NKT 
      cells, and more profound influence on IFNgamma was observed. By adjusting the pH of 
      culture medium we further showed that, dysfunction of NKT cells could simply be 
      induced by low extracellular pH. Moreover, low extracellular pH inhibited NKT 
      cell functions by inhibiting mammalian target of rapamycin (mTOR) signaling and 
      nuclear translocation of promyelocytic leukemia zinc-finger (PLZF). Together, our 
      results suggest that tumor acidic microenvironments could interfere with NKT cell 
      functions through metabolic controls.
FAU - Xie, Di
AU  - Xie D
AD  - CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS Center for 
      Excellence in Molecular Cell Science, School of Life Sciences and Medical Center, 
      University of Science and Technology of China, Hefei, 230027, China.
AD  - Innovation Center for Cell Signaling Network, Hefei National Laboratory for 
      Physical Sciences at Microscale, Hefei, 230027, China.
FAU - Zhu, Shasha
AU  - Zhu S
AD  - CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS Center for 
      Excellence in Molecular Cell Science, School of Life Sciences and Medical Center, 
      University of Science and Technology of China, Hefei, 230027, China.
AD  - Innovation Center for Cell Signaling Network, Hefei National Laboratory for 
      Physical Sciences at Microscale, Hefei, 230027, China.
FAU - Bai, Li
AU  - Bai L
AD  - CAS Key Laboratory of Innate Immunity and Chronic Disease, CAS Center for 
      Excellence in Molecular Cell Science, School of Life Sciences and Medical Center, 
      University of Science and Technology of China, Hefei, 230027, China. 
      baili@ustc.edu.cn.
AD  - Innovation Center for Cell Signaling Network, Hefei National Laboratory for 
      Physical Sciences at Microscale, Hefei, 230027, China. baili@ustc.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20161205
PL  - China
TA  - Sci China Life Sci
JT  - Science China. Life sciences
JID - 101529880
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (Promyelocytic Leukemia Zinc Finger Protein)
RN  - 0 (Zbtb16 protein, mouse)
RN  - 207137-56-2 (Interleukin-4)
RN  - 33X04XA5AT (Lactic Acid)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Active Transport, Cell Nucleus/drug effects
MH  - Animals
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Flow Cytometry
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Interferon-gamma/metabolism
MH  - Interleukin-4/metabolism
MH  - Kruppel-Like Transcription Factors/metabolism
MH  - Lactic Acid/*metabolism/pharmacology
MH  - Mice, Transgenic
MH  - Microscopy, Confocal
MH  - Natural Killer T-Cells/drug effects/*metabolism
MH  - Neoplasms/metabolism/pathology
MH  - Promyelocytic Leukemia Zinc Finger Protein
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - *Tumor Microenvironment
OTO - NOTNLM
OT  - IFNgamma
OT  - NKT cell
OT  - PLZF
OT  - lactic acid
OT  - mTOR
EDAT- 2016/12/21 06:00
MHDA- 2017/07/19 06:00
CRDT- 2016/12/21 06:00
PHST- 2016/11/15 00:00 [received]
PHST- 2016/11/22 00:00 [accepted]
PHST- 2016/12/21 06:00 [entrez]
PHST- 2016/12/21 06:00 [pubmed]
PHST- 2017/07/19 06:00 [medline]
AID - 10.1007/s11427-016-0348-7 [pii]
AID - 10.1007/s11427-016-0348-7 [doi]
PST - ppublish
SO  - Sci China Life Sci. 2016 Dec;59(12):1290-1296. doi: 10.1007/s11427-016-0348-7. 
      Epub 2016 Dec 5.