Anti-tumor experimental study of mouse multi-subtype heat shock protein/peptide vaccine combined with PD-L1 immunological checkpoint inhibitor
10.3969/j.issn.1000-8179.2019.06.337
- VernacularTitle:小鼠多亚型热休克蛋白/肽疫苗联合PD-L1免疫检查点抑制剂的抗肿瘤实验研究*
- Author:
Haojiang LI
1
;
Zhenyong WANG
;
Shi SHEN
;
Chao GAO
;
Bin ZHANG
;
Zeha WANG
;
Xiang SUI
;
Xuemei CUI
;
Mei YUAN
;
Shuoyun LIU
;
Quanyi GUO
;
Guiqin WANG
Author Information
1. 山西医科大学微生物学与免疫学教研室
- Keywords:
multi-subtype heat shock protein/peptide (mHSP/P);
Grp94/peptide (Grp94/P);
chromatography;
PD-L1 immunological checkpoint inhibitor;
IFN-γ;
TNF-α
- From:
Chinese Journal of Clinical Oncology
2019;46(6):278-283
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To evaluate the anti-tumor activity of mouse multi-subtype heat shock protein/peptide (mHSP/P) vaccine in combination with a programmed death ligand 1 (PD-L1) inhibitor in mouse sarcoma. Methods: Immunohistochemical staining and en-zyme-linked immunosorbent assay (Elisa) was used to quantitatively identify the expression of heat shock proteins (HSP70, HSP90, Grp94) in the sarcoma cell line MCA207. From the protein suspension prepared, mHSP/P and Grp94/peptide (Grp94/P) sarcoma vac-cines were isolated using chromatography and were identified by Western blot (WB). Flow cytometry was used to determine their cy-totoxic effects. The levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) produced upon mHSP/P and Grp94/P stimulation were measured by Elisa. The effect of sarcoma vaccines on the growth and survival of sarcoma was evaluated in mice. The expression of PD-L1 on the surface of MCA207 sarcoma cells was evaluated by immunofluorescent staining. The effect of IFN-γ treatment on the expression of PD-L1 was determined by WB. Animal experiments explored the effects of PD-L1 inhibitor in combination with mHSP/P treatment on tumors. Results: Tumor tissue carries a variety of HSP subtypes (HSP70, HSP90, Grp94). We successfully isolated sarco-ma tissue-derived mHSP/P and Grp94/P tumor vaccines, which were identified by WB; flow cytometry analysis demonstrated their cy-totoxicity. The levels of IFN-γ and TNF-α cytokines upon mHSP/P stimulation were significantly higher than that observed upon Grp94/P stimulation (P<0.05). The expression of PD-L1 on the surface of sarcoma cells increased with IFN-γ treatment. Animal experiments demonstrated that PD-L1 inhibitor in combination with mHSP/P significantly increased the immune response against tumor (P<0.05). Conclusions: Tumor-derived mHSP/P and Grp94/P can be used as tumor vaccines in animal models. The mHSP/P can elicit a stronger anti-tumor immune response than Grp94/P. IFN-γ stimulates the expression of PD-L1 in sarcoma cells, which results in immune eva-sion. The PD-L1 inhibitor in combination with mHSP/P increased the anti-tumor effect in the tumor microenvironment.
