Prognostic Impact of Tumor-Infiltrating Lymphocytes and Neutrophils on Survival of Patients with Upfront Resection of Pancreatic Cancer.

Rainer C Miksch,Jens Werner,Florian Bösch,Jan G D’Haese,Barbara Mayer,Maximilian Weniger,Steffen Ormanns,Markus B Schoenberg,Alexandr V Bazhin

doi:10.3390/cancers11010039

Rainer C Miksch, Jens Werner + Show 7 more

Open Access

https://doi.org/10.3390/cancers11010039

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Journal: Cancers	Publication Date: Jan 3, 2019
Citations: 85	License type: CC BY 4.0

Affiliation: Ludwig-Maximilians-Universität München

Abstract

In patients with pancreatic ductal adenocarcinoma (PDAC), the tumor microenvironment consists of cellular and stromal components that influence prognosis. Hence, tumor-infiltrating lymphocytes (TILs) may predict prognosis more precisely than conventional staging systems. Studies on the impact of TILs are heterogeneous and further research is needed. Therefore, this study aims to point out the importance of peritumoral TILs, tumor-infiltrating neutrophils (TINs), and immune subtype classification in PDAC. Material from 57 patients was analyzed with immunohistochemistry performed for CD3, CD8, CD20, CD66b, α-sma, and collagen. Hot spots with peritumoral TILs and TINs were quantified according to the QTiS algorithm and the distance of TILs hot spots to the tumor front was measured. Results were correlated with overall (OS) and progression-free survival (PFS). High densities of peritumoral hot spots with CD3+, CD8+, and CD20+ TILs correlated significantly with improved OS and PFS. Combined immune cell subtypes predicted improved OS and PFS. High infiltration of CD3+ TILs predicted progression after 12 months. The location of TILs’ hot spots and their distance to the tumor front did not correlate with patient survival. Peritumoral TILs and the composition of the stroma predict OS and PFS in PDAC.

Highlights

Pancreatic ductal adenocarcinoma (PDAC) ranks fourth amongst cancer-associated deaths in both men and women [1,2,3,4,5,6]
Fifty seven (57) patients who underwent upfront resection for PDAC were included in this study
We addressed whether both—the immunological stromal composition represented by tumor-infiltrating leukocytes (TILs and tumor-infiltrating neutrophils (TINs)) and the stromal composition represented by collagen and cancer-associated fibroblasts (CAFs) had to be considered to predict survival in patients with PDAC: The density of stromal composition was different among the patients in this study: high density of activated fibroblasts (CAF)

Summary

Introduction

Pancreatic ductal adenocarcinoma (PDAC) ranks fourth amongst cancer-associated deaths in both men and women [1,2,3,4,5,6]. Despite constant efforts to improve treatment, the prognosis remains poor, with an overall five-year survival rate of about 5% [5,7]. This can be attributed to lack of efficient chemoand radiotherapy options, but more importantly, to the presentation of patients mostly in advanced tumor stages [8,9]. PDAC is described primarily by the transformation of exocrine cells to tumor cells [10]. Besides features of PDAC cells themselves, the complex function of the tumor microenvironment (TME) has become increasingly important [11]

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