Z Gastroenterol 2017; 55(05): e1-e27
DOI: 10.1055/s-0037-1603060
Kategorie „Grundlagen-orientierte Forschung“
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   Medizinische Klinik und Poliklinik II, Klinikum der Universität München
2   Department of Medicine A, University Medicine Greifswald
,
E Langhoff
1   Medizinische Klinik und Poliklinik II, Klinikum der Universität München
,
E Costello
3   NIHR Liverpool Pancreas Biomedical Research Centre, University of Liverpool
,
W Greenhalf
3   NIHR Liverpool Pancreas Biomedical Research Centre, University of Liverpool
,
C Halloran
3   NIHR Liverpool Pancreas Biomedical Research Centre, University of Liverpool
,
G Beyer
1   Medizinische Klinik und Poliklinik II, Klinikum der Universität München
2   Department of Medicine A, University Medicine Greifswald
,
FU Weiss
1   Medizinische Klinik und Poliklinik II, Klinikum der Universität München
,
JP Neoptolemos
3   NIHR Liverpool Pancreas Biomedical Research Centre, University of Liverpool
,
MW Büchler
4   Department of General, Visceral and Transplantation Surgery, University of Heidelberg
,
T Kohlmann
5   Department of Community Medicine, University Medicine Greifswald
,
MM Lerch
1   Medizinische Klinik und Poliklinik II, Klinikum der Universität München
,
J Mayerle
1   Medizinische Klinik und Poliklinik II, Klinikum der Universität München
2   Department of Medicine A, University Medicine Greifswald
› Author Affiliations
Further Information

Publication History

Publication Date:
09 May 2017 (online)

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Aim:

Remodelling of the PDAC microenvironment and ECM has been implicated in the prognosis of PDAC. We investigated whether infiltration of immune cell-subsets (CD3, CD4, CD8, CD68, CD206 or neutrophils) affect the survival of pancreatic cancer patients and affect stromal composition (fibrogenic (αSMA high/collagen I high) versus fibrolytic stroma (αSMA high/collagen I low)) and aimed at finding of a comprehensive prognostic signature.

Material & Methods:

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

Results:

In 1824 TMA from 382 patients (94.6%) immune cell composition was distinctly different in fibrolytic versus fibrogenic stroma. Median event free survival (EFS) for patients with high CD3 expression as a single marker was 14.3 months (95% CI 12.7 to 17.3) whereas low CD3 expression predicted significantly decreased survival (11 months, 95% CI 9.9 to 12.7, χ2 LR,1DF= 14.7; P = 0.0001). CD8, CD68 and CD206 expression showed similar trends. Recursive partitioning for discrete-time-survival-tree analysis showed dependence of leukocyte subpopulations in determining fibrogenic vs. fibrolytic stroma and median EFS varied between 6.3 month versus 20.1 month depending on immune cell infiltration and type of stroma.

Discussion:

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