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

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.

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 (

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.

Informations de copyright

Copyright © 2023 Johansen, Novitski, Hjaltelin, Theile, Boisen, Brunak, Madsen, Nielsen and Chen.

Déclaration de conflit d'intérêts

IC: Research Funding: Roche Inst, Bristol Myers Squibb Inst, Celgene Inst, Genis Inst, and Varian Medical Systems Inst; Travel, Accommodation Expenses: Roche, Bristol Myers Squibb, Celgene, and Bayer; Advisory Role: Amgen. SB: Ownership: Intomics A/S, Hoba Therapeutics Aps, Novo Nordisk A/S, Lundbeck A/S, ALK abello A/S; Managing Board Memberships: Proscion A/S and Intomics A/S. The authors declare that this study received funding from the Danish Comprehensive Cancer Center, the Lundbeck Foundation, Varian, and the Novo Nordisk Foundation. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.