한빛사 논문
Kyung Hwan Kim, M.D.1, Jinhyun Cho, M.D.2, Bo Mi Ku, Ph.D.3, Jiae Koh, M.S.3,4, Jong-Mu Sun, M.D.2, Se-Hoon Lee, M.D.2, Jin Seok Ahn, M.D.2, Jaekyung Cheon, M.D.5, Young Joo Min, M.D.5, Su-Hyung Park, Ph.D.1, Keunchil Park, M.D.2, MyungJu Ahn, M.D.2,4,*, Eui-Cheol Shin, Ph.D.1,*
1 Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea
2 Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
3 Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
4 Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea
5 Division of Hematology and Oncology, Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea
*Correspondence to:
Prof. Eui-Cheol Shin, Laboratory of Immunology and Infectious Diseases, Graduate
School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Daejeon 34141, Republic of Korea; Tel. +82-42-350-4236;
Prof. Myung-Ju Ahn, Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro,
Gangnam-gu, Seoul, 06351, Republic of Korea;
Abstract
Purpose: To investigate blood-based dynamic biomarkers that predict responses to anti-PD-1 therapy in solid tumors. Experimental Design: Pre-planned biomarker analysis was performed as part of a phase II clinical trial (NCT02607631)in patients with metastatic or refractory thymic epithelial tumors (TETs; n= 31) who received pembrolizumab. The biomarker was further tested in an independent cohort of prospectively recruited patients with metastatic non-small cell lung cancer (NSCLC) who received pembrolizumab or nivolumab (NSCLC cohort 1; n= 33) and validated in an independent cohort of patients with NSCLC (NSCLC cohort 2; n= 46). Peripheral blood samples were obtained immediately before treatment (D0) and 7 days after the first dose (D7) and analyzed using multi-color flow cytometry. Results: A higher fold-change in the percentage of Ki-67+cells among PD-1+CD+8T cells 7 days after the first dose (Ki-67D07/D0) significantly predicted durable clinical benefit (DCB;P < 0.001) and prolonged progression-free survival (PFS; P=0.027) in patients with TET. Ki-67D7/D0≥ 2.8 was also associated with better DCB, PFS, and overall survival (OS) in NSCLC cohort 1 (all P< 0.05). Ki-D7/D0was subsequently validated in NSCLC cohort 2, and Ki-67D7/D0≥ 2.8 significantly predicted better DCB (P=0.001), PFS (P=0.002), and OS (P=0.037). Ki-67D7/D0had a low correlation with tumor PD-L1 expression and combining both factors did not improve the predictive power of Ki-67D7/D0. Conclusions: The proliferative response of peripheral blood PD-1+CD8+T cells, measured as the fold-change in the percentage of Ki-67+cells 7 days after treatment (Ki-67D7/D0), may be a useful surrogate biomarker for predicting the response and prognosis to anti-PD-1 therapy in solid tumors.
논문정보
관련 링크
연구자 키워드
연구자 ID
관련분야 연구자보기
관련분야 논문보기
해당논문 저자보기