PMID- 35847509
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220719
IS  - 2211-3835 (Print)
IS  - 2211-3843 (Electronic)
IS  - 2211-3835 (Linking)
VI  - 12
IP  - 4
DP  - 2022 Apr
TI  - Targeting tumor endothelial hyperglycolysis enhances immunotherapy through 
      remodeling tumor microenvironment.
PG  - 1825-1839
LID - 10.1016/j.apsb.2022.02.014 [doi]
AB  - Vascular abnormality is a hallmark of most solid tumors and facilitates immune 
      evasion. Targeting the abnormal metabolism of tumor endothelial cells (TECs) may 
      provide an opportunity to improve the outcome of immunotherapy. Here, in 
      comparison to vascular endothelial cells from adjacent peritumoral tissues in 
      patients with colorectal cancer (CRC), TECs presented enhanced glycolysis with 
      higher glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression. Then an 
      unbiased screening identified that osimertinib could modify the GAPDH and thus 
      inhibit its activity in TECs. Low-dose osimertinib treatment caused tumor 
      regression with vascular normalization and increased infiltration of immune 
      effector cells in tumor, which was due to the reduced secretion of lactate from 
      TECs by osimertinib through the inhibition of GAPDH. Moreover, osimertinib and 
      anti-PD-1 blockade synergistically retarded tumor growth. This study provides a 
      potential strategy to enhance immunotherapy by targeting the abnormal metabolism 
      of TECs.
CI  - (c) 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, 
      Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
FAU - Shan, Yunlong
AU  - Shan Y
AD  - Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of 
      Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
FAU - Ni, Qi
AU  - Ni Q
AD  - Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of 
      Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
FAU - Zhang, Qixiang
AU  - Zhang Q
AD  - Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of 
      Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
FAU - Zhang, Mengying
AU  - Zhang M
AD  - Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of 
      Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
FAU - Wei, Bin
AU  - Wei B
AD  - Department of Hematology and Oncology, the Affiliated Huaian No. 1 People's 
      Hospital of Nanjing Medical University, Huai'an 223300, China.
FAU - Cheng, Lingge
AU  - Cheng L
AD  - Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of 
      Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
FAU - Zhong, Chongjin
AU  - Zhong C
AD  - Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of 
      Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
FAU - Wang, Xinyu
AU  - Wang X
AD  - Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of 
      Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
FAU - Wang, Qingqing
AU  - Wang Q
AD  - Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of 
      Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
FAU - Liu, Jiali
AU  - Liu J
AD  - Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of 
      Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
FAU - Zhang, Jingwei
AU  - Zhang J
AD  - Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of 
      Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
FAU - Wu, Jingjing
AU  - Wu J
AD  - Department of Hematology and Oncology, the Affiliated Huaian No. 1 People's 
      Hospital of Nanjing Medical University, Huai'an 223300, China.
FAU - Wang, Guangji
AU  - Wang G
AD  - Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of 
      Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
FAU - Zhou, Fang
AU  - Zhou F
AD  - Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of 
      Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
LA  - eng
PT  - Journal Article
DEP - 20220222
PL  - Netherlands
TA  - Acta Pharm Sin B
JT  - Acta pharmaceutica Sinica. B
JID - 101600560
PMC - PMC9279856
OTO - NOTNLM
OT  - Colorectal cancer
OT  - Endothelial glycolysis
OT  - GAPDH
OT  - Immunometabolism
OT  - Immunotherapy
OT  - Normalized glycolysis
OT  - Osimertinib
OT  - Tumor microenvironment
EDAT- 2022/07/19 06:00
MHDA- 2022/07/19 06:01
PMCR- 2022/02/22
CRDT- 2022/07/18 04:16
PHST- 2021/11/09 00:00 [received]
PHST- 2021/12/17 00:00 [revised]
PHST- 2022/01/20 00:00 [accepted]
PHST- 2022/07/18 04:16 [entrez]
PHST- 2022/07/19 06:00 [pubmed]
PHST- 2022/07/19 06:01 [medline]
PHST- 2022/02/22 00:00 [pmc-release]
AID - S2211-3835(22)00070-3 [pii]
AID - 10.1016/j.apsb.2022.02.014 [doi]
PST - ppublish
SO  - Acta Pharm Sin B. 2022 Apr;12(4):1825-1839. doi: 10.1016/j.apsb.2022.02.014. Epub 
      2022 Feb 22.