Predictive biomarkers for cancer immunotherapy with immune checkpoint inhibitors
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REVIEW
Open Access
Predictive biomarkers for cancer immunotherapy with immune checkpoint inhibitors Rilan Bai, Zheng Lv, Dongsheng Xu and Jiuwei Cui*
Abstract Although the clinical development of immune checkpoint inhibitors (ICIs) therapy has ushered in a new era of antitumor therapy, with sustained responses and significant survival advantages observed in multiple tumors, most patients do not benefit. Therefore, more and more attention has been paid to the identification and development of predictive biomarkers for the response of ICIs, and more in-depth and comprehensive understanding has been continuously explored in recent years. Predictive markers of ICIs efficacy have been gradually explored from the expression of intermolecular interactions within tumor cells to the expression of various molecules and cells in tumor microenvironment, and been extended to the exploration of circulating and host systemic markers. With the development of high-throughput sequencing and microarray technology, a variety of biomarker strategies have been deeply explored and gradually achieved the process from the identification of single marker to the development of multifactorial synergistic predictive markers. Comprehensive predictive-models developed by integrating different types of data based on different components of tumor-host interactions is the direction of future research and will have a profound impact in the field of precision immuno-oncology. In this review, we deeply analyze the exploration course and research progress of predictive biomarkers as an adjunctive tool to tumor immunotherapy in effectively identifying the efficacy of ICIs, and discuss their future directions in achieving precision immuno-oncology. Keywords: Neoplasm, Immune checkpoint inhibitor, Predictive biomarker, Tumor mutation burden, Programmed death ligand-1
Background Immune checkpoint inhibitors (ICIs) therapy has ushered in a new era of anti-tumor therapy, with sustained responses and significant survival advantages observed in multiple tumors. Anti-programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) antibody has been approved for second-line or first-line treatment in a variety of malignant neoplasms, including melanoma, lung cancer, renal cell carcinoma (RCC), head and neck squamous cell carcinoma (HNSCC) and gastroesophageal * Correspondence: [email protected] Cancer Center, the First Hospital of Jilin University, 71 Xinmin Street, Changchun, Jilin 130021, China
cancer [1, 2]. However, despite the breakthrough in clinical treatment with ICIs, most patients do not benefit. Pembrolizumab or nivolumab has an objective response rate (ORR) of 40–45% in first-line melanoma and 20% in second-line non-small cell lung cancer (NSCLC) [3–5]. Therefore, in recent years, more and more attentions have been paid to the identification and development of predictive biomarkers for the efficacy of ICIs, and more indepth and comprehensive understanding has also been obtained in recent years, including new data on biomarkers of tumor genome
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