PD-1 antibody enhanced anti-tumor efficacy of oxaliplatin against colon cancer in vitro and in vivo
10.3872/j.issn.1007-385X.2018.10.005
- VernacularTitle:PD-1抗体增强奥沙利铂体内外抗结肠癌的效果
- Author:
ZHONG Genshen1a
1
;
SUN Zhiyang1a
2
;
CHEN Yanan1a
2
;
XU Zhishan1c
3
;
YANG Ru1c
3
;
WU Minna1d
4
;
SHI Huan2
5
;
LU Ping1a
2
Author Information
1. 1a. Department II of Oncology, the First Affiliated Hospital； 1b. Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Laboratory Medicine
2. 1a. Department II of Oncology, the First Affiliated Hospital
3. Research Centre of Life Science and Technology, the FirstAffiliated Hospital
4. Department of Microbiology, College of Basic Medicine, Xinxiang Medical University
5. . Department of Oncology, Shandong Cancer HospitalAffiliated to Shandong University
- Publication Type:Journal Article
- Keywords:
oxaliplatin (OXA);
PD-1 antibody;
colon cancer;
CD8+ T cell
- From:
Chinese Journal of Cancer Biotherapy
2018;25(10):999-1005
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To explore the anti-tumor effects of oxaliplatin (OXA) combined with PD-1 antibody on colon cancer. Methods: Flow cytometry was used to detect the expression of PD-L1 in colon cancer cell lines HCT-116 and HT-29. Co-culture method was used to detect the secretion of cytokines and the changes of CD4/CD8 subsets in T-cells that co-cultured with HCT-116 cells, which were pretreated with OXAin combination with/without PD-1 antibody; The CT26 transplanted tumor model of colon cancer in BALB/c mice was established and treated with the combination of OXA and PD-1 to evaluate their anti-tumor efficacy. Meanwhile, CD8 antibody was used to scavenge CD8+ T cells in mice, and to evaluate the role of CD8+ T cells in the anti-tumor effect of OXA in vivo. Results: OXAcould significantly increase the expression of PD-L1 on the surface of colon cancer cells. Compared with pure T-cells, the T cells co-cultured with colon cancer HCT-116 cells that pre-treated by OXA, exhibited significantly reduced IL-2, IFN-γ and TNF levels (all P<0.05) in its culture supernatant and decreased ratio of CD4+memory T cell / CD8+TEMER (P<0.05), whereas there was increased cell proportion of the CD4+ (P>0.05) and CD8+ (P<0.05) naïve T cells. After co-treated with PD-1 antibody, compared with the single treatment of OXA, IFN-γ and IL-10 content (P<0.05) in culture supernatant and the subsets of CD8+ TCM and TEMRA ratio (P>0.05) were increased. In vivo experiments showed that OXAcombined with PD-1 antibody could enhance its anti-tumor activity, the tumor suppression rates were 25.6% (OXA) and 29.1% (αPD-1), respectively, however, the rate of tumor inhibition was increased to 58.2% when combined (P<0.05, compared to OXA or αPD-1 group). After scavenging CD8+T cells in mice, the antitumor activity of OXA dropped from 68.4% to 46.2% (P<0.05). Conclusion: OXA combined with PD-1 antibody had synergistic anti-tumor effect, and CD8+ T cells played an important role in the antitumor activity of OXA.
- Full text:20181005.txt
