The potential predictive value of circulating immune cell ratio and tumor marker in atezolizumab treated advanced non-small cell lung cancer patients

Article type: Research Article

Authors: Zhuo, Minglei^{a; b; 1} | Chen, Hanxiao^{a; b; 1} | Zhang, Tianzhuo^c | Yang, Xue^{a; b} | Zhong, Jia^{a; b} | Wang, Yuyan^{a; b} | An, Tongtong^{a; b} | Wu, Meina^{a; b} | Wang, Ziping^{a; b} | Huang, Jing^{c; *} | Zhao, Jun^{a; b; *}

Affiliations: [a] Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing, China | [b] Department of Thoracic Medical Oncology, Peking University Cancer Hospital and Institute, Beijing 100142, China | [c] Department of Immunology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China

Correspondence: [*] Corresponding author: Jing Huang, Center for Human Disease Genomics, Peking University Health Science Center, No. 38 Xueyuan Road, Haidian District, Beijing 100191, China. E-mail: huangjing82@bjmu.edu.cn.JunZhao,DepartmentofThoracicMedicalOncology,PekingUniversityCancerHospitalandInstitute,No.52FuchengRoad,HaidianDistrict,Beijing100142,China.Tel.:+861088196456;Fax:+861088196562;E-mail:ohjerry@163.com.

Note: [1] Authors contributed equally to this article.

Abstract: BACKGROUND: The PD-L1 antibody atezolizumab has shown promising efficacy in patients with advanced non-small cell lung cancer. But the predictive marker of clinical benefit has not been identified. OBJECTIVE: This study aimed to search for potential predictive factors in circulating blood of patients receiving atezolizumab. METHODS: Ten patients diagnosed with advanced non-small cell lung cancer were enrolled in this open-label observing study. Circulating immune cells and plasma tumor markers were examined in peripheral blood from these patients before and after atezolizumab treatment respectively. Relation between changes in circulating factors and anti-tumor efficacy were analyzed. RESULTS: Blood routine test showed that atezolizumab therapy induced slightly elevation of white blood cells count generally. The lymphocyte ratio was increased slightly in disease controlled patients but decreased prominently in disease progressed patients in response to atezolizumab therapy. Flow cytometric analysis revealed changes in percentage of various immune cell types, including CD4+ T cell, CD8+ T cell, myeloid-derived suppressor cell, regulatory T cell and PD-1 expressing T cell after atezolizumab. Levels of plasma tumor marker CEA, CA125 and CA199 were also altered after anti-PD-L1 therapy. In comparison with baseline, the disease progressed patients showed sharp increase in tumor marker levels, while those disease controlled patients were seen with decreased regulatory T cell and myeloid-derived suppressor cell ratios. CONCLUSIONS: The circulating immune cell ratios and plasma tumor marker levels were related with clinical efficacy of atezolizumab therapy. These factors could be potential predictive marker for anti-PD-L1 therapy in advanced non-small cell lung cancer.

Keywords: Circulating immune cell, immunotherapy, non-small cell lung cancer, PD-L1, tumor marker

DOI: 10.3233/CBM-171089

Journal: Cancer Biomarkers, vol. 22, no. 3, pp. 467-476, 2018