AUTHOR=Kurosaki Takashi , Chamoto Kenji , Suzuki Shinichiro , Kanemura Hiroaki , Mitani Seiichiro , Tanaka Kaoru , Kawakami Hisato , Kishimoto Yo , Haku Yasuharu , Ito Katsuhiro , Sato Toshiyuki , Suminaka Chihiro , Yamaki Mami , Chiba Yasutaka , Yaguchi Tomonori , Omori Koichi , Kobayashi Takashi , Nakagawa Kazuhiko , Honjo Tasuku , Hayashi Hidetoshi 

TITLE=The combination of soluble forms of PD-1 and PD-L1 as a predictive marker of PD-1 blockade in patients with advanced cancers: a multicenter retrospective study

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1325462

DOI=10.3389/fimmu.2023.1325462

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>The clinical relevance of soluble forms of programmed cell death-1 (sPD-1) and programmed cell death-ligand 1 (sPD-L1) remains unclear. We here investigated the relation between the efficacy of PD-1 blockade and pretreatment plasma levels of sPD-1 and sPD-L1 across a broad range of cancer types.</p></sec><sec><title>Methods</title><p>We retrospectively analyzed clinical data from 171 patients with advanced solid tumors who received nivolumab or pembrolizumab monotherapy regardless of treatment line. The concentrations of sPD-1 and sPD-L1 were measured with a fully automated immunoassay (HISCL system).</p></sec><sec><title>Results</title><p>The study subjects comprised patients with head and neck cancer (<italic>n</italic> = 50), urothelial cancer (<italic>n</italic> = 42), renal cell cancer (<italic>n</italic> = 37), gastric cancer (<italic>n</italic> = 20), esophageal cancer (<italic>n</italic> = 10), malignant pleural mesothelioma (<italic>n</italic> = 6), or microsatellite instability-high tumors (<italic>n</italic> = 6). High or low levels of sPD-1 or sPD-L1 were not significantly associated with progression-free survival (PFS) or overall survival (OS) for PD-1 blockade in the entire study population. Comparison of treatment outcomes according to combinations of high or low sPD-1 and sPD-L1 levels, however, revealed that patients with low sPD-1 and high sPD-L1 concentrations had a significantly poorer PFS (HR of 1.79 [95% CI, 1.13–2.83], <italic>p</italic> = 0.01) and a tendency toward poorer OS (HR of 1.70 [95% CI, 0.99–2.91], <italic>p</italic> = 0.05) compared with all other patients.</p></sec><sec><title>Conclusion</title><p>Our findings suggest that the combination of low sPD-1 and high sPD-L1 levels is a potential negative biomarker for PD-1 blockade therapy.</p></sec>