title: Potential biomarker for checkpoint blockade immunotherapy and treatment strategy.
abstract: Programmed cell death protein-1 (PD-1) and ligand (PD-L1) provide an important escape mechanism from immune attack, and blockade therapy of these proteins show promising clinical benefits in many types of cancer. PD-L1 can be induced by interferon-gamma (IFN-γ), hypoxia, or toll-like receptor (TLR)-mediated pathways that confer adaptive immune resistance, or upregulated by oncogenic signals leading to constitutive expression and resulting in intrinsic immune resistance. The PD-1/PD-L1 checkpoint blockade, which targets regulatory pathways in T cells to overcome immune resistance, is correlated to PD-L1 expression pattern and the presence of tumor-infiltrating lymphocytes (TILs). Meanwhile, immunogenic mutation loads show significant response to checkpoint blockade, which is probably due to PD-1/L1 status and TIL content. Finally, the clinical strategies to design effective checkpoint-targeting immunotherapies are based on the classification of inducible/constitutive expression of PD-L1 and the presence of TILs.
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, 106 Zhongshan Er Rd, Guangzhou, 510080, China.|Southern Medical University, Guangzhou, China.
authors.forename: Zhong-Yi
authors.initials: ZY
authors.lastname: Dong
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, 106 Zhongshan Er Rd, Guangzhou, 510080, China.
authors.forename: Si-Pei
authors.initials: SP
authors.lastname: Wu
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, 106 Zhongshan Er Rd, Guangzhou, 510080, China.
authors.forename: Ri-Qiang
authors.initials: RQ
authors.lastname: Liao
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, 106 Zhongshan Er Rd, Guangzhou, 510080, China.|Southern Medical University, Guangzhou, China.
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: Huang
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, 106 Zhongshan Er Rd, Guangzhou, 510080, China. syylwu@live.cn.
authors.forename: Yi-Long
authors.initials: YL
authors.lastname: Wu
mesh_terms: D060890:B7-H1 Antigen / Q000096:biosynthesis / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007167:Immunotherapy; D007371:Interferon-gamma / Q000627:therapeutic use; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D061026:Programmed Cell Death 1 Receptor / Q000096:biosynthesis / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D051193:Toll-Like Receptors; D007371:Interferon-gamma
keywords: Checkpoint blockade; Immune resistance; Immunotherapy; PD-L1; TILs; Treatment strategy