PMID- 29538621
OWN - NLM
STAT- MEDLINE
DCOM- 20190128
LR  - 20211204
IS  - 1460-2180 (Electronic)
IS  - 0143-3334 (Linking)
VI  - 39
IP  - 5
DP  - 2018 May 3
TI  - Disrupting CD47-SIRPalpha axis alone or combined with autophagy depletion for the 
      therapy of glioblastoma.
PG  - 689-699
LID - 10.1093/carcin/bgy041 [doi]
AB  - CD47-targeting immune checkpoint inhibitors have been investigated for 
      immunotherapy of several cancers, glioblastoma, one of the most common tumors in 
      brain, was still a challenge for CD47-targeting therapy. Herein, we reported 
      novel strategies for glioblastoma therapy via blocking CD47-signal regulatory 
      protein-alpha (SIRPalpha) by SIRPalpha-Fc alone or in combination with autophagy inhibition. 
      Our results showed that SIRPalpha-Fc increased macrophages-triggered cytotoxicity and 
      phagocytosis of glioblastoma cells then elicited potent anti-tumor efficacy. 
      During the treatment, SIRPalpha-Fc induced autophagy and autophagic flux in 
      glioblastoma cells and Akt/mammalian target of rapamycin (mTOR) inactivation was 
      participated in the autophagy activation. Inhibition of autophagy by 
      pharmacological agents or small-interfering RNA increased SIRPalpha-Fc-triggered 
      macrophage phagocytosis and cytotoxicity. Importantly, when compared with 
      SIRPalpha-Fc treatment, blocking both CD47/SIRPalpha and autophagy significantly 
      increased infiltration of macrophages and apoptosis of tumor cells, triggering 
      potentiated anti-glioblastoma effect and extended median survival. Further 
      experiments showed that adaptive immune response, including CD8+ T-cell subsets, 
      was also played a crucial role in SIRPalpha-Fc-induced glioblastoma rejection. Our 
      results indicated that SIRPalpha-Fc alone or combined with autophagy inhibitors 
      elicited potent anti-glioblastoma effect, highlighting potential therapeutic 
      strategies of glioblastoma via blocking CD47/SIRPalpha alone or in combination with 
      autophagy inhibitor.
FAU - Zhang, Xuyao
AU  - Zhang X
AD  - Department of Microbiological and Biochemical Pharmacy, The Key Laboratory of 
      Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, 
      Shanghai, China.
FAU - Chen, Wei
AU  - Chen W
AD  - Department of Microbiological and Biochemical Pharmacy, The Key Laboratory of 
      Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, 
      Shanghai, China.
FAU - Fan, Jiajun
AU  - Fan J
AD  - Department of Microbiological and Biochemical Pharmacy, The Key Laboratory of 
      Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, 
      Shanghai, China.
FAU - Wang, Shaofei
AU  - Wang S
AD  - Department of Microbiological and Biochemical Pharmacy, The Key Laboratory of 
      Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, 
      Shanghai, China.
AD  - Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
FAU - Xian, Zongshu
AU  - Xian Z
AD  - Department of Microbiological and Biochemical Pharmacy, The Key Laboratory of 
      Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, 
      Shanghai, China.
FAU - Luan, Jingyun
AU  - Luan J
AD  - Department of Microbiological and Biochemical Pharmacy, The Key Laboratory of 
      Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, 
      Shanghai, China.
FAU - Li, Yubin
AU  - Li Y
AD  - Department of Microbiological and Biochemical Pharmacy, The Key Laboratory of 
      Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, 
      Shanghai, China.
AD  - Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
FAU - Wang, Yichen
AU  - Wang Y
AD  - Department of Microbiological and Biochemical Pharmacy, The Key Laboratory of 
      Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, 
      Shanghai, China.
FAU - Nan, Yanyang
AU  - Nan Y
AD  - Department of Microbiological and Biochemical Pharmacy, The Key Laboratory of 
      Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, 
      Shanghai, China.
FAU - Luo, Man
AU  - Luo M
AD  - Department of Microbiological and Biochemical Pharmacy, The Key Laboratory of 
      Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, 
      Shanghai, China.
FAU - Li, Song
AU  - Li S
AD  - ImmuneOnco Biopharma (Shanghai) Co., Ltd., Shanghai, China.
FAU - Tian, Wenzhi
AU  - Tian W
AD  - ImmuneOnco Biopharma (Shanghai) Co., Ltd., Shanghai, China.
FAU - Ju, Dianwen
AU  - Ju D
AD  - Department of Microbiological and Biochemical Pharmacy, The Key Laboratory of 
      Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, 
      Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (CD47 Antigen)
RN  - 0 (Receptors, Immunologic)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Autophagy/*immunology
MH  - CD47 Antigen/*metabolism
MH  - CD8-Positive T-Lymphocytes/immunology/metabolism
MH  - Cell Line, Tumor
MH  - Glioblastoma/immunology/*metabolism/*therapy
MH  - Humans
MH  - Immunotherapy/methods
MH  - Macrophages/immunology
MH  - Mice
MH  - Phagocytosis/immunology
MH  - Receptors, Immunologic/*metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
EDAT- 2018/03/15 06:00
MHDA- 2019/01/29 06:00
CRDT- 2018/03/15 06:00
PHST- 2017/09/25 00:00 [received]
PHST- 2018/03/08 00:00 [accepted]
PHST- 2018/03/15 06:00 [pubmed]
PHST- 2019/01/29 06:00 [medline]
PHST- 2018/03/15 06:00 [entrez]
AID - 4925742 [pii]
AID - 10.1093/carcin/bgy041 [doi]
PST - ppublish
SO  - Carcinogenesis. 2018 May 3;39(5):689-699. doi: 10.1093/carcin/bgy041.