1509P - Cytokines and ductal pancreatic adenocarcinoma: Exploring their relationship with prognosis and molecular subtypes

Background

The lack of effective predictive biomarkers remains a major challenge in the management of patients (pt) with pancreatic ductal adenocarcinoma (PDAC). Tumor microenvironment and cytokines play an important role in the prognosis of pt with PDAC. Furthermore, the simultaneous analysis of molecular subtypes of PDAC may also allow the establishment of a correlation between certain cytokines and the molecular subtype.

Methods

This is a retrospective observational study. We included all pt with PDAC from whom a plasma sample had been collected before starting the first chemotherapy treatment at La Paz University Hospital between 2016 and 2022. We measured the plasma levels of the following cytokines by a bead-based fluorescence multiplex assay: TGF-β1-3, IL-1α, IL-1β, IL-6, IL-8, IL-9, IL-10, IP-10, IL-15, IL-17A and TNF-α. The expression of GATA6 and CK17 were tested by immunohistochemistry.

Results

A total of 73 pt were included. The increase in levels of IL-1α, IL-1β, IL-6, IL-8, IL-9, and IL-15 was associated with a higher risk of progression during first-line (1L). In addition, the increase in levels of these cytokines together with TGF-β1 and TNF-α was associated with a higher risk of mortality. Higher percentiles (p) of IL-1β, IL-6 were associated with shorter PFS during 1L and higher p of IL-6, IL-8, and TNF-α were correlated with shorter OS. Multivariate analysis showed that IL-8 levels were independently associated with increased risk of progression during 1L and with mortality (Table). Elevated levels of TGF-β2 were associated with basal-like and null subtypes (p=0.040) and increased levels of IL-17A were correlated with classical and mixed subtypes (p=0.021). In the multivariate analysis, TGF-β2 levels were independently associated with basal-like and null subtypes. Table: 1509P