Serum IL-6 as a prognostic biomarker and IL-6R as a therapeutic target in biliary tract cancers.

Serum IL-6 as a prognostic biomarker and IL-6R as a therapeutic target in biliary tract cancers.:

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Serum IL-6 as a prognostic biomarker and IL-6R as a therapeutic target in biliary tract cancers.

Clin Cancer Res. 2020 Sep 15;:

Authors: Hogdall DTS, O'Rourke CJ, Dehlendorff C, Larsen FO, Jensen LH, Johansen AZ, Dang H, Factor VM, Grunnet M, Mau-Sørensen M, Oliveira DVNP, Linnemann D, Boisen MK, Wang XW, Johansen JS, Andersen JB

Abstract

PURPOSE: Biliary tract cancers (BTC) are a rare heterogeneous disease with dismal prognosis often associated with inflammation. We assessed the prognostic value of IL-6 and YKL-40 compared to CA19-9 before and during palliative chemotherapy. We also investigated in mice if IL-6R inhibition in combination with gemcitabine could prolong chemosensitivity.

EXPERIMENTAL DESIGN: 452 Danish participants with advanced (locally advanced and metastatic) BTC were included from six clinical trials (February 2004 to March 2017). Serum CA19-9, IL-6 and YKL-40 were measured before and during palliative treatment. Associations between candidate biomarkers and progression-free survival (PFS) and overall survival (OS) were analyzed by univariate and multivariate Cox regression. Effects of inhibiting IL-6R and YKL-40 were assessed in vitro, and of IL-6R inhibition in vivo.

RESULTS: High pre-treatment CA19-9, IL-6 and YKL-40, and increasing levels during treatment, were associated with short PFS and OS in patients with advanced BTC. IL-6 provided independent prognostic information independent of tumor location and in patients with normal serum CA19-9. ROC analyses showed that IL-6 and YKL-40 were predictive of very short OS (OS<6 months), whereas CA19-9 was best to predict OS >1.5 years. Treatment with anti-IL-6R and gemcitabine significantly diminished tumor growth when compared with gemcitabine monotherapy in an in vivo transplant model of BTC.

CONCLUSIONS: Serum IL-6 and YKL-40 are potential new prognostic biomarkers in BTC. IL-6 provides independent prognostic information and may be superior to CA19-9 in certain contexts. Moreover, anti-IL-6R should be considered as a new treatment option to sustain gemcitabine response in BTC patients.



PMID: 32933994 [PubMed - as supplied by publisher]