Kiyohiro Ando1,2, Kazuyuki Hamada3, Midori Shida1,2, Ryotaro Ohkuma1,2,3, Yutaro Kubota3, Atsushi Horiike3, Hiroto Matsui3, Tomoyuki Ishiguro3, Yuya Hirasawa3, Hirotsugu Ariizumi3, Makoto Watanabe1,2, Rie Onoue1,2, Junji Tsurutani3,4, Kiyoshi Yoshimura2,3, Takuya Tsunoda3, Shinichi Kobayashi2, Satoshi Wada5,6,7. 1. Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, 6-11-11 Kita-Karasuyama, Setagaya-ku, Tokyo, 157-8577, Japan. 2. Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, 6-11-11 Kita-Karasuyama, Setagaya-ku, Tokyo, 157-8577, Japan. 3. Department of Medicine, Division of Medical Oncology, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan. 4. Advanced Cancer Translational Research Institute, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan. 5. Department of Clinical Diagnostic Oncology, Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, 6-11-11 Kita-Karasuyama, Setagaya-ku, Tokyo, 157-8577, Japan. st-wada@med.showa-u.ac.jp. 6. Clinical Research Institute for Clinical Pharmacology and Therapeutics, Showa University, 6-11-11 Kita-Karasuyama, Setagaya-ku, Tokyo, 157-8577, Japan. st-wada@med.showa-u.ac.jp. 7. Department of Medicine, Division of Medical Oncology, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, 142-8555, Japan. st-wada@med.showa-u.ac.jp.
Abstract
PURPOSE: Targeting of anti-programmed cell death protein-1 (PD-1) and anti-programmed death-ligand 1 (PD-L1) is a standard therapeutic strategy for various cancers. The aim of the present study was to investigate the prognostic effect of pretreatment PD-L1 expression levels in peripheral blood mononuclear cell (PBMC) subsets for patients with several cancer types receiving anti-PD-1 blockade therapies. PATIENTS AND METHODS: Thirty-two patients undergoing anti-PD-L1 blockade therapy, including 15 with non-small cell lung cancer, 14 with gastric cancer, 1 with melanoma, 1 with parotid cancer, and 1 with bladder cancer, were recruited for the present study. PD-L1 expression levels in CD3+, CD4+, CD8+, CD45RA+ and CCR7+ T cells; CD20+ B cells; CD14+ and CD16+ monocytes were measured via flow cytometry before treatment. The percentages of PD-L1+ cells in respective PBMC subsets were compared with respect to different clinicopathological conditions and the association with overall survival (OS) was assessed. RESULTS: The percentages of PD-L1+ with CD3+, CD4+ and CD8+ T cells including naïve and memory T cell subsets, or CD20+ B cells during pretreatment were not markedly correlated with the OS of patients (p > 0.05); however, the percentage of the PD-L1+ CD14+ monocyte subset was significantly correlated with OS (p = 0.0426). CONCLUSION: Increase in pretreatment expression levels of PD-L1 on CD14+ monocytes is associated with the OS of patients treated with immune checkpoint inhibitors. Further evaluation of large sample size and each specific cancer type might clarify the predictive role of PBMC in patients.
PURPOSE: Targeting of anti-programmed cell death protein-1 (PD-1) and anti-programmed death-ligand 1 (PD-L1) is a standard therapeutic strategy for various cancers. The aim of the present study was to investigate the prognostic effect of pretreatment PD-L1 expression levels in peripheral blood mononuclear cell (PBMC) subsets for patients with several cancer types receiving anti-PD-1 blockade therapies. PATIENTS AND METHODS: Thirty-two patients undergoing anti-PD-L1 blockade therapy, including 15 with non-small cell lung cancer, 14 with gastric cancer, 1 with melanoma, 1 with parotid cancer, and 1 with bladder cancer, were recruited for the present study. PD-L1 expression levels in CD3+, CD4+, CD8+, CD45RA+ and CCR7+ T cells; CD20+ B cells; CD14+ and CD16+ monocytes were measured via flow cytometry before treatment. The percentages of PD-L1+ cells in respective PBMC subsets were compared with respect to different clinicopathological conditions and the association with overall survival (OS) was assessed. RESULTS: The percentages of PD-L1+ with CD3+, CD4+ and CD8+ T cells including naïve and memory T cell subsets, or CD20+ B cells during pretreatment were not markedly correlated with the OS of patients (p > 0.05); however, the percentage of the PD-L1+ CD14+ monocyte subset was significantly correlated with OS (p = 0.0426). CONCLUSION: Increase in pretreatment expression levels of PD-L1 on CD14+ monocytes is associated with the OS of patients treated with immune checkpoint inhibitors. Further evaluation of large sample size and each specific cancer type might clarify the predictive role of PBMC in patients.
Authors: Daniel L Barber; E John Wherry; David Masopust; Baogong Zhu; James P Allison; Arlene H Sharpe; Gordon J Freeman; Rafi Ahmed Journal: Nature Date: 2005-12-28 Impact factor: 49.962
Authors: Suzanne L Topalian; F Stephen Hodi; Julie R Brahmer; Scott N Gettinger; David C Smith; David F McDermott; John D Powderly; Richard D Carvajal; Jeffrey A Sosman; Michael B Atkins; Philip D Leming; David R Spigel; Scott J Antonia; Leora Horn; Charles G Drake; Drew M Pardoll; Lieping Chen; William H Sharfman; Robert A Anders; Janis M Taube; Tracee L McMiller; Haiying Xu; Alan J Korman; Maria Jure-Kunkel; Shruti Agrawal; Daniel McDonald; Georgia D Kollia; Ashok Gupta; Jon M Wigginton; Mario Sznol Journal: N Engl J Med Date: 2012-06-02 Impact factor: 91.245
Authors: Charles S Fuchs; Toshihiko Doi; Raymond W Jang; Kei Muro; Taroh Satoh; Manuela Machado; Weijing Sun; Shadia I Jalal; Manish A Shah; Jean-Phillipe Metges; Marcelo Garrido; Talia Golan; Mario Mandala; Zev A Wainberg; Daniel V Catenacci; Atsushi Ohtsu; Kohei Shitara; Ravit Geva; Jonathan Bleeker; Andrew H Ko; Geoffrey Ku; Philip Philip; Peter C Enzinger; Yung-Jue Bang; Diane Levitan; Jiangdian Wang; Minori Rosales; Rita P Dalal; Harry H Yoon Journal: JAMA Oncol Date: 2018-05-10 Impact factor: 31.777