SBRT combined with PD-1/PD-L1 inhibitors in NSCLC treatment: a focus on the mechanisms, advances, and future challenges

• Published in: Journal of hematology and oncology 2020-07, Vol.13 (1), p.105-17, Article 105
• Main Authors: Chen, Yu, Gao, Min, Huang, Zhaoqin, Yu, Jinming, Meng, Xiangjiao
• Format: Article
• Language: English
• Subjects: Advances; Antigens, Neoplasm - immunology; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Antineoplastic Agents, Immunological - adverse effects; Antineoplastic Agents, Immunological - therapeutic use; Antitumor activity; Apoptosis; Atezolizumab; B cells; B7-H1 Antigen - antagonists & inhibitors; B7-H1 Antigen - physiology; Biomarkers; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - immunology; Carcinoma, Non-Small-Cell Lung - radiotherapy; Cell death; Challenges; Chemotaxis, Leukocyte - radiation effects; Clinical trials; Clinical Trials as Topic; Combination treatment; Combined Modality Therapy; Deoxyribonucleic acid; DNA; Drug Resistance, Neoplasm; Gene expression; Hematology; Humans; Immune checkpoint inhibitors; Immune Checkpoint Inhibitors - adverse effects; Immune Checkpoint Inhibitors - therapeutic use; Immune response; Immunity - radiation effects; Immunotherapy; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - immunology; Lung Neoplasms - radiotherapy; Lymphocytes; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - radiation effects; Medical prognosis; Metastasis; Multicenter Studies as Topic; Neoplasm Proteins - antagonists & inhibitors; Non-small cell lung cancer; Non-small cell lung carcinoma; Non-small-cell lung cancer (NSCLC); Oncology; PD-1 protein; PD-1/PD-L1 inhibitors; PD-L1 protein; Pembrolizumab; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Programmed Cell Death 1 Receptor - physiology; Progression-Free Survival; Radiation (Physics); Radiation Dose Hypofractionation; Radiation therapy; Radiosurgery - adverse effects; Radiosurgery - methods; Radiotherapy; Radiotherapy Planning, Computer-Assisted; Review; Small cell lung carcinoma; Solid tumors; Stereotactic body radiation therapy (SBRT); T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - radiation effects; Treatment Outcome; Tumor Escape; Tumors
• ISSN: 1756-8722; 1756-8722
• DOI: 10.1186/s13045-020-00940-z

Immune checkpoint inhibitors targeting programmed cell death 1 (PD-1), programmed cell death ligand-1 (PD-L1), and others have shown potent clinical efficacy and have revolutionized the treatment protocols of a broad spectrum of tumor types, especially non-small-cell lung cancer (NSCLC). Despite the substantial optimism of treatment with PD-1/PD-L1 inhibitors, there is still a large proportion of patients with advanced NSCLC who are resistant to the inhibitors. Preclinical and clinical trials have demonstrated that radiotherapy can induce a systemic antitumor immune response and have a great potential to sensitize refractory "cold" tumors to immunotherapy. Stereotactic body radiation therapy (SBRT), as a novel radiotherapy modality that delivers higher doses to smaller target lesions, has shown favorable antitumor effects with significantly improved local and distant control as well as better survival benefits in various solid tumors. Notably, research has revealed that SBRT is superior to conventional radiotherapy, possibly because of its more powerful immune activation effects. Thus, PD-1/PD-L1 inhibitors combined with SBRT instead of conventional radiotherapy might be more promising to fight against NSCLC, further achieving more favorable survival outcomes. In this review, we focus on the underlying mechanisms and recent advances of SBRT combined with PD-1/PD-L1 inhibitors with an emphasis on some future challenges and directions that warrant further investigation.