AUTHOR=Johansen Astrid Z. , Novitski Sif I. , Hjaltelin Jessica X. , Theile Susann , Boisen Mogens K. , Brunak Søren , Madsen Daniel H. , Nielsen Dorte L. , Chen Inna M. 

TITLE=Plasma YKL-40 is associated with prognosis in patients with metastatic pancreatic cancer receiving immune checkpoint inhibitors in combination with radiotherapy

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1228907

DOI=10.3389/fimmu.2023.1228907

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>YKL-40, also known as chitinase-3-like protein 1 (CHI3L1), is a secreted glycoprotein produced by various cell types including stromal, immune, and cancer cells. It contributes to cancer progression through tumor-promoting inflammation and has been shown to inhibit the cytotoxicity of T and NK lymphocytes. <italic>In vivo</italic> studies have demonstrated synergistic anti-cancer effects of blocking YKL-40 in combination with immune checkpoint inhibitors (ICIs). Biomarkers for the prediction of the response to ICIs are highly needed. We investigated the association between plasma YKL-40 and clinical benefit and survival in patients with metastatic pancreatic cancer (mPC) receiving ICIs and stereotactic body radiotherapy (SBRT).</p></sec><sec><title>Methods</title><p>Blood samples were collected from 84 patients with mPC who participated in the randomized phase II CheckPAC study, in which patients received nivolumab with or without ipilimumab combined with a single fraction of SBRT. Plasma YKL-40 was measured using a commercial ELISA kit.</p></sec><sec><title>Results</title><p>Elevated baseline plasma YKL-40 was an independent predictor of shorter overall survival (OS) (HR 2.19, 95% CI 1.21–3.95). A ≥ 40% decrease in plasma YKL-40 during treatment was associated with longer progression-free survival (<italic>p</italic> = 0.009) and OS (<italic>p</italic> = 0.0028). There was no correlation between plasma YKL-40 and the tumor burden marker CA19-9 at baseline or during treatment.</p></sec><sec><title>Conclusion</title><p>This study contributes new knowledge regarding YKL-40 as a predictor of clinical benefit from ICIs and radiotherapy. These exploratory results warrant further investigation of YKL-40 as a biomarker for patients treated with immunotherapies.</p></sec><sec><title>Clinical trial registration</title><p><uri xlink:href="https://clinicaltrials.gov/" xmlns:xlink="http://www.w3.org/1999/xlink">Clinicaltrials.gov</uri>, identifier NCT02866383.</p></sec>