Targeting DNA Repair Response Promotes Immunotherapy in Ovarian Cancer: Rationale and Clinical Application

被引:10
作者
Xie, Hongyu [1 ,2 ]
Wang, Wenjie [3 ]
Qi, Wencai [4 ]
Jin, Weilin [5 ]
Xia, Bairong [4 ]
机构
[1] Zhejiang Univ, Clin Res Ctr, Womens Hosp, Sch Med, Hangzhou, Peoples R China
[2] Harbin Med Univ, Dept Gynecol Oncol, Canc Hosp, Harbin, Peoples R China
[3] Harbin Med Univ, Sch Publ Hlth, Dept Epidmiol & Biostat, Harbin, Peoples R China
[4] Univ Sci & Technol, Dept Gynecol Oncol, Div Life Sci & Med, Affiliated Hosp 1, Hefei, Peoples R China
[5] Lanzhou Univ, Inst Canc Neurosci, Med Frontier Innovat Res Ctr, Clin Med Coll 1,Hosp 1, Lanzhou, Peoples R China
来源
FRONTIERS IN IMMUNOLOGY | 2021年 / 12卷
基金
中国国家自然科学基金;
关键词
ovarian cancer; DNA damage response; PARP inhibitors; combination therapy; immune checkpoint inhibitors (ICI); TUMOR-INFILTRATING LYMPHOCYTES; REGULATES PD-L1 EXPRESSION; HOMOLOGOUS RECOMBINATION; EXCISION-REPAIR; MUTATIONAL BURDEN; PARP INHIBITORS; NEOANTIGEN LOAD; OPEN-LABEL; DAMAGE; CELLS;
D O I
10.3389/fimmu.2021.661115
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Immune checkpoint inhibitors (ICI) have emerged as a powerful oncologic treatment modality for patients with different solid tumors. Unfortunately, the efficacy of ICI monotherapy in ovarian cancer is limited, and combination therapy provides a new opportunity for immunotherapy in ovarian cancer. DNA damage repair (DDR) pathways play central roles in the maintenance of genomic integrity and promote the progression of cancer. A deficiency in DDR genes can cause different degrees of DNA damage that enhance local antigen release, resulting in systemic antitumor immune responses. Thus, the combination of DDR inhibitors with ICI represents an attractive therapeutic strategy with the potential to improve the clinical outcomes of patients with ovarian cancer. In this review, we provide an overview of the interconnectivity between DDR pathway deficiency and immune response, summarize available clinical trials on the combination therapy in ovarian cancer, and discuss the potential predictive biomarkers that can be utilized to guide the use of combination therapy.
引用
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页数:12
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