PMID- 34491338
OWN - NLM
STAT- MEDLINE
DCOM- 20220506
LR  - 20220506
IS  - 1460-2377 (Electronic)
IS  - 0953-8178 (Linking)
VI  - 34
IP  - 3
DP  - 2022 Feb 23
TI  - Pharmacological effects on anaplerotic pathways alter the metabolic landscape in 
      the tumor microenvironment, causing unpredictable, sustained anti-tumor immunity.
PG  - 133-140
LID - 10.1093/intimm/dxab067 [doi]
AB  - To achieve sustained anti-tumor immunity, tumor-infiltrating effector CD8 T 
      lymphocytes (CD8 TILs) must be able to produce cytokines, including IFNgamma, and 
      proliferate robustly within the local tumor tissue upon antigen recognition. IFNgamma 
      production by CD8 TILs depends on glycolysis, whereas their proliferation 
      additionally requires oxidative phosphorylation (OxPhos). The level of OxPhos, 
      and hence the oxygen consumption rate, depends on mitochondrial biogenesis and 
      requires the loading of metabolic precursors into the tricarboxylic acid cycle to 
      keep it functioning. This is referred to as anaplerosis. Recent advances in the 
      field of immuno-metabolism have shown the impact of pharmacological agents on 
      anaplerotic pathways, resulting in metabolic down-regulation in tumor cells; in 
      contrast, the agents trigger sustained anti-tumor immunity by up-regulating both 
      glycolysis and OxPhos in CD8 TILs. The opposing effects of pharmacological 
      inhibition (and/or activation) on anaplerosis in tumor cells and CD8 TILs are 
      unpredictable. Careful dissection of the underlying mechanism might confer 
      important knowledge, helping us to step into a new era for cancer immunotherapy.
CI  - (c) The Japanese Society for Immunology. 2021. All rights reserved. For 
      permissions, please e-mail: journals.permissions@oup.com.
FAU - Udono, Heiichiro
AU  - Udono H
AD  - Department of Immunology, Okayama University Graduate School of Medicine, 
      Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 
      Japan.
FAU - Nishida, Mikako
AU  - Nishida M
AD  - Department of Immunology, Okayama University Graduate School of Medicine, 
      Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 
      Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Int Immunol
JT  - International immunology
JID - 8916182
SB  - IM
MH  - CD8-Positive T-Lymphocytes
MH  - Glycolysis
MH  - Immunotherapy
MH  - *Lymphocytes, Tumor-Infiltrating
MH  - *Tumor Microenvironment
OTO - NOTNLM
OT  - immuno-metabolism
OT  - tumor immunity
EDAT- 2021/09/08 06:00
MHDA- 2022/05/07 06:00
CRDT- 2021/09/07 12:31
PHST- 2021/08/06 00:00 [received]
PHST- 2021/09/06 00:00 [accepted]
PHST- 2021/09/08 06:00 [pubmed]
PHST- 2022/05/07 06:00 [medline]
PHST- 2021/09/07 12:31 [entrez]
AID - 6365959 [pii]
AID - 10.1093/intimm/dxab067 [doi]
PST - ppublish
SO  - Int Immunol. 2022 Feb 23;34(3):133-140. doi: 10.1093/intimm/dxab067.