Tubeimoside-1 induces TFEB-dependent lysosomal degradation of PD-L1 and promotes antitumor immunity by targeting mTOR.
10.1016/j.apsb.2021.03.039
- Author:
Xiaojia LIU
1
;
Mingxiao YIN
1
;
Jingwen DONG
1
;
Genxiang MAO
2
;
Wenjian MIN
3
;
Zean KUANG
1
;
Peng YANG
3
;
Lu LIU
4
;
Na ZHANG
1
;
Hongbin DENG
1
Author Information
1. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
2. Zhejiang Provincial Key Lab of Geriatrics, Department of Geriatrics, Zhejiang Hospital, Hangzhou 310013, China.
3. State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
4. Qingdao Women and Children's Hospital, Qingdao University, Qingdao 266034, China.
- Publication Type:Journal Article
- Keywords:
4EBP1, eIF4E-binding protein 1;
Baf, bafilomycin A1;
CETSA, cellular thermal shift assay;
CHX, cycloheximide;
CQ, chloroquine;
IB, immunoblotting;
ICB, immune checkpoint blockade;
IHC, immunohistochemistry;
Immune checkpoint blockade;
LLC, Lewis lung carcinoma;
Lysosome;
MDSCs, myeloid-derived suppressor cells;
NAG, β-N-acetylglucosaminidase;
NSCLC, non-small cell lung cancer;
PD-1, programmed cell death-1;
PD-L1;
PD-L1, programmed cell death ligand- 1;
SPR, surface plasmon resonance;
TBM-1, tubeimoside-1;
TFEB, nuclear transcriptional factor EB;
TILs, tumor-infiltrating lymphocytes;
Transcription factor EB;
Tregs, regulatory T-lymphocytes;
mTOR;
mTOR, mammalian target of rapamycin;
p70S6K, phosphorylation of p70 S6 kinase;
qRT-PCR, quantitative real-time polymerase chain reaction
- From:
Acta Pharmaceutica Sinica B
2021;11(10):3134-3149
- CountryChina
- Language:English
-
Abstract:
Programmed cell death ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) cascade is an effective therapeutic target for immune checkpoint blockade (ICB) therapy. Targeting PD-L1/PD-1 axis by small-molecule drug is an attractive approach to enhance antitumor immunity. Using flow cytometry-based assay, we identify tubeimoside-1 (TBM-1) as a promising antitumor immune modulator that negatively regulates PD-L1 level. TBM-1 disrupts PD-1/PD-L1 interaction and enhances the cytotoxicity of T cells toward cancer cells through decreasing the abundance of PD-L1. Furthermore, TBM-1 exerts its antitumor effect in mice bearing Lewis lung carcinoma (LLC) and B16 melanoma tumor xenograft
