PMID- 29226090
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2212-1366 (Print)
IS  - 2212-1374 (Electronic)
IS  - 2212-1366 (Linking)
VI  - 9
DP  - 2017 Nov
TI  - Inhibition of IL-18-mediated myeloid derived suppressor cell accumulation 
      enhances anti-PD1 efficacy against osteosarcoma cancer.
PG  - 59-64
LID - 10.1016/j.jbo.2017.10.002 [doi]
AB  - Myeloid derived suppressor cells (MDSC) are very important in tumor immune 
      evasion and they dramatically increased in peripheral blood of patients with 
      osteosarcoma cancer. The association between MDSC and various cytokines has been 
      studied in the peripheral blood. However, little is known about the mechanism 
      drawing MDSC into tumor parenchyma. This study was to analyze the correlation 
      between MDSC subsets and interleukin 18 (IL-18) level in osteosarcoma tumor model 
      and its effect on the immunotherapy. MDSC were isolated from the blood and 
      parenchyma and analyzed in the osteosarcoma tumor model. IL-18 levels were 
      detected by enzyme-linked immunosorbent assay (ELISA) assay, real-time PCR, 
      western blot and flow cytometry. Moreover, combination treatment with IL-18 
      inhibition and anti-PD1 was conducted to assess the therapeutic effects of IL-18 
      blockade. Results showed MDSC levels had a positive correlation with IL-18, 
      suggesting IL-18 may attract MDSC into the parenchyma. IL-18 gene and protein 
      expression significantly increased in blood and tumor lysates of tumor-bearing 
      mice. Anti-IL-18 treatment significantly decreased G-MDSC and M-MDSC in the 
      peripheral blood and tumor. Furthermore, combination therapy decreased the tumor 
      burden and increased CD4(+) and CD8(+) T cell infiltration, as well as the 
      production of interferon gamma (IFNgamma) and granzyme B. Our study revealed a 
      possible correlation between MDSC subsets and IL-18 inducing MDSC migration into 
      the tumor tissue, in addition to provide the potential target to enhance the 
      efficacy of immunotherapy in patients with osteosarcoma.
FAU - Guan, Ying
AU  - Guan Y
AD  - Department of Orthopedics, the First Affiliated Hospital of Harbin Medical 
      University, Harbin 150001, PR China.
FAU - Zhang, Rui
AU  - Zhang R
AD  - Department of Neurology, General Hospital of Heilongjiang Province Land 
      Reclamation Headquarter, Harbin 150001, PR China.
FAU - Peng, Zhibin
AU  - Peng Z
AD  - Department of Orthopedics, the First Affiliated Hospital of Harbin Medical 
      University, Harbin 150001, PR China.
FAU - Dong, Daming
AU  - Dong D
AD  - Department of Orthopedics, the First Affiliated Hospital of Harbin Medical 
      University, Harbin 150001, PR China.
FAU - Wei, Guojun
AU  - Wei G
AD  - Department of Orthopedics, the First Affiliated Hospital of Harbin Medical 
      University, Harbin 150001, PR China.
FAU - Wang, Yansong
AU  - Wang Y
AD  - Department of Orthopedics, the First Affiliated Hospital of Harbin Medical 
      University, Harbin 150001, PR China.
LA  - eng
PT  - Journal Article
DEP - 20171101
PL  - Netherlands
TA  - J Bone Oncol
JT  - Journal of bone oncology
JID - 101610292
PMC - PMC5715437
OTO - NOTNLM
OT  - Anti-PD1
OT  - IL-18
OT  - Myeloid derived suppressor cells
OT  - Osteosarcoma
EDAT- 2017/12/12 06:00
MHDA- 2017/12/12 06:01
PMCR- 2017/11/01
CRDT- 2017/12/12 06:00
PHST- 2017/09/06 00:00 [received]
PHST- 2017/10/24 00:00 [revised]
PHST- 2017/10/29 00:00 [accepted]
PHST- 2017/12/12 06:00 [entrez]
PHST- 2017/12/12 06:00 [pubmed]
PHST- 2017/12/12 06:01 [medline]
PHST- 2017/11/01 00:00 [pmc-release]
AID - S2212-1374(17)30098-2 [pii]
AID - 10.1016/j.jbo.2017.10.002 [doi]
PST - epublish
SO  - J Bone Oncol. 2017 Nov 1;9:59-64. doi: 10.1016/j.jbo.2017.10.002. eCollection 
      2017 Nov.