The developing landscape of combinatorial therapies of immune checkpoint blockade with DNA damage repair inhibitors for the treatment of breast and ovarian cancers |
| |
Authors: | Zhu Lingling Liu Jiewei Chen Jiang Zhou Qinghua |
| |
Affiliation: | 1.Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China, 410008 ;2.Key Laboratory for Molecular Radiation Oncology of Hunan Province, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China, 410008 ;3.National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China ; |
| |
Abstract: | In this era of precision medicine, with the help of biomarkers, immunotherapy has significantly improved prognosis of many patients with malignant tumor. Deficient mismatch repair (dMMR)/microsatellite instability (MSI) status is used as a biomarker in clinical practice to predict favorable response to immunotherapy and prognosis. MSI is an important characteristic which facilitates mutation and improves the likelihood of a favorable response to immunotherapy. However, many patients with dMMR/MSI still respond poorly to immunotherapies, which partly results from intratumor heterogeneity propelled by dMMR/MSI. In this review, we discuss how dMMR/MSI facilitates mutations in tumor cells and generates intratumor heterogeneity, especially through type II interferon (IFN-γ) signaling and tumor-infiltrating lymphocytes (TILs). We discuss the mechanism of immunotherapy from the perspective of dMMR/MSI, molecular pathways and TILs, and we discuss how intratumor heterogeneity hinders the therapeutic effect of immunotherapy. Finally, we summarize present techniques and strategies to look at the tumor as a whole to design personalized regimes and achieve favorable prognosis. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|