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

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2019 Jan 6

PMID 30609853

Citations 55

Authors

Rainer C Miksch

Markus B Schoenberg

Maximilian Weniger

Florian Bosch

Steffen Ormanns

Barbara Mayer

Jens Werner

Alexandr V Bazhin

Jan G DHaese

Affiliations

Soon will be listed here.

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.

Citing Articles

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References

Talamini G, Bassi C, Falconi M, Sartori N, Salvia R, Rigo L . Alcohol and smoking as risk factors in chronic pancreatitis and pancreatic cancer. Dig Dis Sci. 1999; 44(7):1303-11. DOI: 10.1023/a:1026670911955. View

Maxwell P, McCluggage W . Audit and internal quality control in immunohistochemistry. J Clin Pathol. 2001; 53(12):929-32. PMC: 1731142. DOI: 10.1136/jcp.53.12.929. View

Fukunaga A, Miyamoto M, Cho Y, Murakami S, Kawarada Y, Oshikiri T . CD8+ tumor-infiltrating lymphocytes together with CD4+ tumor-infiltrating lymphocytes and dendritic cells improve the prognosis of patients with pancreatic adenocarcinoma. Pancreas. 2004; 28(1):e26-31. DOI: 10.1097/00006676-200401000-00023. View

Qiu D, Kurosawa M, Lin Y, Inaba Y, Matsuba T, Kikuchi S . Overview of the epidemiology of pancreatic cancer focusing on the JACC Study. J Epidemiol. 2005; 15 Suppl 2:S157-67. PMC: 8639044. DOI: 10.2188/jea.15.s157. View

Hiraoka N, Onozato K, Kosuge T, Hirohashi S . Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions. Clin Cancer Res. 2006; 12(18):5423-34. DOI: 10.1158/1078-0432.CCR-06-0369. View

Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Mlecnik B, Lagorce-Pages C . Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006; 313(5795):1960-4. DOI: 10.1126/science.1129139. View

Faul F, Erdfelder E, Lang A, Buchner A . G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007; 39(2):175-91. DOI: 10.3758/bf03193146. View

Kyndi M, Sorensen F, Knudsen H, Overgaard M, Nielsen H, Andersen J . Tissue microarrays compared with whole sections and biochemical analyses. A subgroup analysis of DBCG 82 b&c. Acta Oncol. 2008; 47(4):591-9. DOI: 10.1080/02841860701851871. View

Erkan M, Michalski C, Rieder S, Reiser-Erkan C, Abiatari I, Kolb A . The activated stroma index is a novel and independent prognostic marker in pancreatic ductal adenocarcinoma. Clin Gastroenterol Hepatol. 2008; 6(10):1155-61. DOI: 10.1016/j.cgh.2008.05.006. View

10.

Raimondi S, Maisonneuve P, Lowenfels A . Epidemiology of pancreatic cancer: an overview. Nat Rev Gastroenterol Hepatol. 2009; 6(12):699-708. DOI: 10.1038/nrgastro.2009.177. View

11.

Faul F, Erdfelder E, Buchner A, Lang A . Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods. 2009; 41(4):1149-60. DOI: 10.3758/BRM.41.4.1149. View

12.

Yadav D, Whitcomb D . The role of alcohol and smoking in pancreatitis. Nat Rev Gastroenterol Hepatol. 2010; 7(3):131-45. DOI: 10.1038/nrgastro.2010.6. View

13.

Eckel-Passow J, Lohse C, Sheinin Y, Crispen P, Krco C, Kwon E . Tissue microarrays: one size does not fit all. Diagn Pathol. 2010; 5:48. PMC: 2910003. DOI: 10.1186/1746-1596-5-48. View

14.

Gooden M, de Bock G, Leffers N, Daemen T, Nijman H . The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis. Br J Cancer. 2011; 105(1):93-103. PMC: 3137407. DOI: 10.1038/bjc.2011.189. View

15.

Reid M, Basturk O, Thirabanjasak D, Hruban R, Klimstra D, Bagci P . Tumor-infiltrating neutrophils in pancreatic neoplasia. Mod Pathol. 2011; 24(12):1612-9. PMC: 3227778. DOI: 10.1038/modpathol.2011.113. View

16.

Tjomsland V, Niklasson L, Sandstrom P, Borch K, Druid H, Bratthall C . The desmoplastic stroma plays an essential role in the accumulation and modulation of infiltrated immune cells in pancreatic adenocarcinoma. Clin Dev Immunol. 2011; 2011:212810. PMC: 3235447. DOI: 10.1155/2011/212810. View

17.

Galon J, Pages F, Marincola F, Thurin M, Trinchieri G, Fox B . The immune score as a new possible approach for the classification of cancer. J Transl Med. 2012; 10:1. PMC: 3269368. DOI: 10.1186/1479-5876-10-1. View

18.

Siegel R, Naishadham D, Jemal A . Cancer statistics, 2012. CA Cancer J Clin. 2012; 62(1):10-29. DOI: 10.3322/caac.20138. View

19.

Erkan M, Hausmann S, Michalski C, Fingerle A, Dobritz M, Kleeff J . The role of stroma in pancreatic cancer: diagnostic and therapeutic implications. Nat Rev Gastroenterol Hepatol. 2012; 9(8):454-67. DOI: 10.1038/nrgastro.2012.115. View

20.

Hartwig W, Werner J, Buchler M . Prognosis of resected pancreatic cancer: is the refined resection margin status dispensable?. Langenbecks Arch Surg. 2012; 397(6):859-60. DOI: 10.1007/s00423-012-0968-y. View