Evolution of the immune landscape during progression of pancreatic intraductal papillary mucinous neoplasms to invasive cancer.

Aged Female Humans Male Middle Aged Neoplasm Invasiveness Pancreatic Intraductal Neoplasms / immunology T-Lymphocyte Subsets / immunology Tumor Microenvironment / immunology
Intraductal papillary mucinous neoplasm Pancreatic cancer Premalignant lesion Tumour immunology Tumour microenvironment

Journal

EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039

Informations de publication

Date de publication:
Apr 2020
Historique:
received: 08 12 2019
revised: 10 02 2020
accepted: 27 02 2020
pubmed: 8 4 2020
medline: 26 1 2021
entrez: 8 4 2020
Statut: ppublish

Résumé

Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions of pancreatic cancer, which is characterized by an immunosuppressive microenvironment. Yet, the spatial distribution of the immune infiltrate and how it changes during IPMN progression is just beginning to be understood. We obtained tissue samples from patients who underwent pancreatic surgery for IPMN, and performed comprehensive immunohistochemical analyses to investigate the clinical significance, composition and spatial organization of the immune microenvironment during progression of IPMNs. Survival analysis of pancreatic cancer patients was stratified by tumour infiltrating immune cell subtypes. The immune microenvironment evolves from a diverse T cell mixture, comprising CD8 The major change with regards to T cell composition during IPMN progression occurs at the step of tissue invasion, indicating that malignant transformation only occurs when tumour immune surveillance is overcome. This suggests that novel immunotherapies that would boost spontaneous antitumor immunity at premalignant states could prevent pancreatic cancer development. The present work was supported by German Cancer Aid grants (70,112,720 and 70,113,167) to S. R., and the Olympia Morata Programme of the Medical Faculty of Heidelberg University to S. R.

Sections du résumé

BACKGROUND BACKGROUND
Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions of pancreatic cancer, which is characterized by an immunosuppressive microenvironment. Yet, the spatial distribution of the immune infiltrate and how it changes during IPMN progression is just beginning to be understood.
METHODS METHODS
We obtained tissue samples from patients who underwent pancreatic surgery for IPMN, and performed comprehensive immunohistochemical analyses to investigate the clinical significance, composition and spatial organization of the immune microenvironment during progression of IPMNs. Survival analysis of pancreatic cancer patients was stratified by tumour infiltrating immune cell subtypes.
FINDINGS RESULTS
The immune microenvironment evolves from a diverse T cell mixture, comprising CD8
INTERPRETATION CONCLUSIONS
The major change with regards to T cell composition during IPMN progression occurs at the step of tissue invasion, indicating that malignant transformation only occurs when tumour immune surveillance is overcome. This suggests that novel immunotherapies that would boost spontaneous antitumor immunity at premalignant states could prevent pancreatic cancer development.
FUNDING BACKGROUND
The present work was supported by German Cancer Aid grants (70,112,720 and 70,113,167) to S. R., and the Olympia Morata Programme of the Medical Faculty of Heidelberg University to S. R.

Identifiants

DOI: 10.1016/j.ebiom.2020.102714 PMID: 32259711 PMC: PMC7132171
pubmed: 32259711
pii: S2352-3964(20)30089-X
doi: 10.1016/j.ebiom.2020.102714
pmc: PMC7132171
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

102714

Informations de copyright

Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare no potential conflicts of interest.

Références

Cancer Cell. 2014 May 12;25(5):621-37
pubmed: 24823639
Am J Surg Pathol. 2004 Aug;28(8):977-87
pubmed: 15252303
Cancer Immunol Res. 2017 Nov;5(11):978-991
pubmed: 29066497
J Exp Med. 2017 Jul 3;214(7):1861-1876
pubmed: 28630089
Oncogene. 2008 Oct 6;27(45):5920-31
pubmed: 18836473
Immunity. 2014 May 15;40(5):772-784
pubmed: 24816405
Cancer Immunol Res. 2014 Jul;2(7):616-31
pubmed: 24942756
Clin Cancer Res. 2018 Sep 15;24(18):4444-4454
pubmed: 29661773
Ann Surg. 2015 Nov;262(5):875-80; discussion 880-1
pubmed: 26583679
Gut. 2016 Oct;65(10):1710-20
pubmed: 26156960
Nat Med. 2015 Nov;21(11):1337-43
pubmed: 26479921
Immunol Rev. 2016 May;271(1):260-75
pubmed: 27088920
J Exp Med. 2011 Mar 14;208(3):469-78
pubmed: 21339327
Br J Cancer. 2015 May 26;112(11):1782-90
pubmed: 25942397
Biomed Res Int. 2017;2017:2831056
pubmed: 28349057
Ann Surg. 2015 May;261(5):976-83
pubmed: 24979607
Cytometry A. 2019 Jun;95(6):647-654
pubmed: 30714682
Clin Cancer Res. 2006 Sep 15;12(18):5423-34
pubmed: 17000676
Gut. 2017 Mar;66(3):495-506
pubmed: 26743012
Gastroenterology. 2013 Nov;145(5):1121-32
pubmed: 23891972
Cancer Cell. 2018 Jun 11;33(6):1048-1060.e7
pubmed: 29894691
Proc Natl Acad Sci U S A. 2019 Jan 29;116(5):1692-1697
pubmed: 30635425
Pancreas. 2014 Apr;43(3):470-7
pubmed: 24622082
J Allergy Clin Immunol. 2015 Mar;135(3):626-35
pubmed: 25528359
Nat Commun. 2019 Mar 29;10(1):1424
pubmed: 30926808
Nature. 2017 Nov 23;551(7681):512-516
pubmed: 29132146
Cancer Discov. 2016 Mar;6(3):270-85
pubmed: 26715645
CA Cancer J Clin. 2019 Jan;69(1):7-34
pubmed: 30620402
Oncoimmunology. 2015 Sep 11;5(4):e1085147
pubmed: 27141376
Clin Cancer Res. 2019 Apr 1;25(7):2194-2205
pubmed: 30385653
Pancreas. 2004 Jan;28(1):e26-31
pubmed: 14707745
Am J Surg Pathol. 2015 Dec;39(12):1730-41
pubmed: 26559377
J Exp Med. 1998 Dec 21;188(12):2357-68
pubmed: 9858522
Immunity. 2018 Apr 17;48(4):812-830.e14
pubmed: 29628290
Cancer Res. 2018 Jun 15;78(12):3293-3305
pubmed: 29572224
Immunity. 2015 Sep 15;43(3):579-90
pubmed: 26341400
Pathology. 2003 Feb;35(1):14-24
pubmed: 12701679
Cancer Res. 2007 Oct 1;67(19):9518-27
pubmed: 17909062
Br J Cancer. 2013 Mar 5;108(4):914-23
pubmed: 23385730
Clin Gastroenterol Hepatol. 2010 Sep;8(9):806-11
pubmed: 20621679
Clin Dev Immunol. 2011;2011:212810
pubmed: 22190968
Immunity. 1998 Sep;9(3):325-36
pubmed: 9768752
Gastroenterology. 2011 Jan;140(1):310-21
pubmed: 20955708
Gut. 2014 Nov;63(11):1769-81
pubmed: 24555999
Pancreatology. 2010;10(5):631-40
pubmed: 21051918
J Clin Invest. 2012 Nov;122(11):4160-71
pubmed: 23064366

Auteurs

Susanne Roth (S)

Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany. Electronic address: susanne.roth@med.uni-heidelberg.de.

Katharina Zamzow (K)

Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany.

Matthias M Gaida (MM)

Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany; Institute of Pathology, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany.

Mathias Heikenwälder (M)

Division of Chronic Inflammation and Cancer, German Cancer Research Center, Heidelberg, Germany.

Christine Tjaden (C)

Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany.

Ulf Hinz (U)

Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany.

Promita Bose (P)

Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany.

Christoph W Michalski (CW)

Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany; Department of Surgery, Halle University Hospital, Halle (Saale), Germany.

Thilo Hackert (T)

Department of Surgery, Heidelberg University Hospital, Heidelberg, Germany.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Evolution of the immune landscape during...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Evolution of the immune landscape during...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Evolution of the immune landscape during...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Invasion tumorale › Evolution of the immune landscape during...
questionsmedicales.fr › Maladies endocriniennes › Tumeurs des glandes endocrines › Tumeurs du pancréas › Tumeurs intracanalaires pancréatiques › Evolution of the immune landscape during...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Sous-populations de lymphocytes T › Evolution of the immune landscape during...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Microenvironnement cellulaire › Microenvironnement tumoral › Evolution of the immune landscape during...