Z Gastroenterol 2017; 55(08): e57-e299
DOI: 10.1055/s-0037-1604945
Kurzvorträge
Pankreas
Prädiktion und Überleben beim Pankreaskarzinom: Freitag, 15 September 2017, 13:00 – 14:28, Coventry/Forschungsforum 4
Georg Thieme Verlag KG Stuttgart · New York

A comprehensive prognostic signature based on interaction of immune cell infiltration with stromal composition for resected pancreatic ductal adenocarcinoma

UM Mahajan
1   Klinikum der LMU München-Grosshadern, Medizinische Klinik und Poliklinik II, München, Deutschland
2   Universitätsmedizin Greifswald, KIM-A, Greifswald, Deutschland
,
E Langhoff
2   Universitätsmedizin Greifswald, KIM-A, Greifswald, Deutschland
,
E Costello
3   NIHR Liverpool Pancreas Biomedical Research Centre, University of Liverpool, Liverpool, Vereinigtes Königreich
,
W Greenhalf
3   NIHR Liverpool Pancreas Biomedical Research Centre, University of Liverpool, Liverpool, Vereinigtes Königreich
,
C Holloran
3   NIHR Liverpool Pancreas Biomedical Research Centre, University of Liverpool, Liverpool, Vereinigtes Königreich
,
G Beyer
1   Klinikum der LMU München-Grosshadern, Medizinische Klinik und Poliklinik II, München, Deutschland
2   Universitätsmedizin Greifswald, KIM-A, Greifswald, Deutschland
,
FU Weiss
2   Universitätsmedizin Greifswald, KIM-A, Greifswald, Deutschland
,
J Neoptolomos
3   NIHR Liverpool Pancreas Biomedical Research Centre, University of Liverpool, Liverpool, Vereinigtes Königreich
,
MW Büchler
4   Universität Heidelberg, Department of General, Visceral and Transplantation Surgery, Heidelburg, Deutschland
,
T Kohlmann
5   Universitätsmedizin Greifswald, Department of Community Medicine, Greifswald, Deutschland
,
MM Lerch
2   Universitätsmedizin Greifswald, KIM-A, Greifswald, Deutschland
,
J Mayerle
1   Klinikum der LMU München-Grosshadern, Medizinische Klinik und Poliklinik II, München, Deutschland
2   Universitätsmedizin Greifswald, KIM-A, Greifswald, Deutschland
› Author Affiliations
Further Information

Publication History

Publication Date:
02 August 2017 (online)

Also available at
 

Aim:

Remodelling of the pancreatic cancer tumour (PDAC) microenvironment and extracellular matrix (ECM) has been implicated in the prognosis of PDAC. We investigated whether infiltration of immune cell subsets affect the survival of pancreatic cancer patients and affect stromal composition (fibrogenic (aSMA high/collagen-I high); fibrolytic stroma (aSMA high/collagen-I low).

Material and methods:

TMA of 404 patients from the ESPAC-3 trial were immunostained for αSMA, collagen-I, CD3, CD4, CD8, CD68, CD206 and neutrophils. Median H-Scores of individual staining were calculated for all cores by multiplying the integrated density of tumor cell staining. Event free survival was plotted against low/high expression of leukocytes using Kaplan-Meier-curves, log-rank-tests, and Cox-proportional-hazards-models. All statistical tests were two-sided and performed in R.

Results:

In 1824 TMA from 382 patients (94.6%) immune cell composition was distinctly different in fibrolytic versus fibrogenic stroma. CD3 (Median EFS high-CD3-expression: 14.3 months vs. CD3-low-expreeesion 11 months, c2 LR,1DF= 14.7; p = 0.0001) count were found as stroma type independent prognostic markers while CD206 and CD68 were dependent on the type of stroma. Recursive partitioning for discrete-time-survival-tree analysis showed CD3 as strongest independent predictor but macrophage subpopulations to determine fibrogenic or fibrolytic stroma with a median EFS ranging from 6.3 month (fibrolytic stroma with low-CD3 and high-CD68 count) to 20.1 month (fibrogenic stroma, CD3-high).

Discussion:

The comprehensive prognostic signature based on interaction of immune cell infiltration with stromal composition provides better stratification in predicting event free survival in PDAC. Immune cells determine the predominant type of stromal composition and this may help in understanding the effect of the host immune response.