title: Radiotherapy combined with immune checkpoint blockade immunotherapy: Achievements and challenges.
abstract: To date, several kinds of immunomodulating monoclonal antibodies (mAbs) have been applied in clinical trials, such as anti-cytotoxic T-lymphocyte antigen-4 (anti-CTLA-4) mAb and anti-programmed death-1 (anti-PD-1) mAb. With the recent success of cancer immunotherapy, especially the checkpoint inhibitors, the renewed interest in immunotherapy as a treatment modality has gained extensive attention. The irradiated tumor cell death can enhance antitumor immunity by inducing antigen expression on tumor cells and activating lymphocytes. Radiotherapy (RT) combined with immunotherapy has revealed promising outcomes in various animal models. However, this new paradigm is often considered as a medical spectacle without a unifying model, and its mechanisms have yet to be elucidated. The purpose of this review is to investigate previously published studies of radiotherapy combined with checkpoint blockades by the following aspects: exploring the potential mechanisms; identifying the most beneficial dose, fraction and target site for RT; finding an appropriate time window to combine these two treatments; and discussing the toxicity and suitable treatment evaluating criteria.
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong University, Jinan, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Teng
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong University, Jinan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Kong
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong University, Jinan, China.
authors.forename: Xiangjiao
authors.initials: X
authors.lastname: Meng
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong University, Jinan, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong University, Jinan, China. Electronic address: sdyujinming@126.com.
authors.forename: Jinming
authors.initials: J
authors.lastname: Yu
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods*; D019583:Dose Fractionation, Radiation; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents
keywords: CTLA-4; Cancer treatment; Checkpoint; Immunotherapy; PD-L1; Radiotherapy