TY - JOUR

T1 - Plasma YKL-40 is associated with prognosis in patients with metastatic pancreatic cancer receiving immune checkpoint inhibitors in combination with radiotherapy

AU - Johansen, Astrid Z.

AU - Novitski, Sif I.

AU - Hjaltelin, Jessica X.

AU - Theile, Susann

AU - Boisen, Mogens K.

AU - Brunak, Søren

AU - Madsen, Daniel H.

AU - Nielsen, Dorte L.

AU - Chen, Inna M.

N1 - Publisher Copyright: Copyright © 2023 Johansen, Novitski, Hjaltelin, Theile, Boisen, Brunak, Madsen, Nielsen and Chen.

PY - 2023

Y1 - 2023

N2 - Background: 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. In vivo 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). Methods: 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. Results: 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 (p = 0.009) and OS (p = 0.0028). There was no correlation between plasma YKL-40 and the tumor burden marker CA19-9 at baseline or during treatment. Conclusion: 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. Clinical trial registration: Clinicaltrials.gov, identifier NCT02866383.

AB - Background: 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. In vivo 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). Methods: 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. Results: 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 (p = 0.009) and OS (p = 0.0028). There was no correlation between plasma YKL-40 and the tumor burden marker CA19-9 at baseline or during treatment. Conclusion: 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. Clinical trial registration: Clinicaltrials.gov, identifier NCT02866383.

KW - biomarker

KW - CHI3L1

KW - immune checkpoint inhibition

KW - pancreatic cancer

KW - YKL-40

U2 - 10.3389/fimmu.2023.1228907

DO - 10.3389/fimmu.2023.1228907

M3 - Journal article

C2 - 37744345

AN - SCOPUS:85171897555

VL - 14

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

M1 - 1228907

ER -