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Topographical Distribution and Spatial Interactions of Innate and Semi-Innate Immune Cells in Pancreatic and Other Periampullary Adenocarcinoma

Lundgren, Sebastian LU ; Micke, Patrick ; Elebro, Jacob LU ; Heby, Margareta LU ; Hrynchyk, Ina ; Nodin, Björn LU ; Leandersson, Karin LU orcid ; Mezheyeuski, Artur and Jirström, Karin LU orcid (2020) In Frontiers in Immunology 11.
Abstract

Background: The clinical management of pancreatic and other periampullary neoplasms remains challenging. In contrast to other cancer types, immunotherapies are largely ineffective, and the reason for the deprived immune response and the immune inhibiting cellular composition is only fragmentarily understood. The aim of this study was to comprehensively map the abundance, topographic distribution and spatial interaction of innate and innate-like immune cells in the tumor microenvironment of periampullary adenocarcinoma. Methods: Multiplexed immunofluorescent imaging was performed on tissue microarrays with tumors from a consecutive cohort of 175 patients with resected periampullary adenocarcinoma. To obtain a detailed spatial analysis of... (More)

Background: The clinical management of pancreatic and other periampullary neoplasms remains challenging. In contrast to other cancer types, immunotherapies are largely ineffective, and the reason for the deprived immune response and the immune inhibiting cellular composition is only fragmentarily understood. The aim of this study was to comprehensively map the abundance, topographic distribution and spatial interaction of innate and innate-like immune cells in the tumor microenvironment of periampullary adenocarcinoma. Methods: Multiplexed immunofluorescent imaging was performed on tissue microarrays with tumors from a consecutive cohort of 175 patients with resected periampullary adenocarcinoma. To obtain a detailed spatial analysis of immune cell infiltration, two multiplex immune panels including antibodies against CD3, NKp46, CD56, CD68, CD163 and CD1a, CD208, CD123, CD15, CD68 and pan-cytokeratin were applied. Results: The infiltration of natural killer (NK) and NK-like T (NKT) cells was lower in malignant compared to benign tissue. NKT cells were more abundant in intestinal type compared to pancreatobiliary type tumors, and were associated with more favorable clinicopathological features and a prolonged survival. The interaction of NKp46+ NKT cells with macrophages was also associated with a prolonged survival. Conclusions: This study provides a comprehensive map of the innate immune landscape in periampullary adenocarcinoma. NK cells, and even more so NKT cells, are revealed to be central players in the local immune response in a clinically relevant context.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
dendritic cells, innate immunity, natural killer cells, natural killer T-cells, tumor microenvironment
in
Frontiers in Immunology
volume
11
article number
558169
publisher
Frontiers Media S. A.
external identifiers
  • pmid:33013928
  • scopus:85091487862
ISSN
1664-3224
DOI
10.3389/fimmu.2020.558169
language
English
LU publication?
yes
id
d899f190-a781-4444-ba2e-f99f75b4f608
date added to LUP
2020-10-27 11:29:53
date last changed
2024-04-03 13:38:09
@article{d899f190-a781-4444-ba2e-f99f75b4f608,
  abstract     = {{<p>Background: The clinical management of pancreatic and other periampullary neoplasms remains challenging. In contrast to other cancer types, immunotherapies are largely ineffective, and the reason for the deprived immune response and the immune inhibiting cellular composition is only fragmentarily understood. The aim of this study was to comprehensively map the abundance, topographic distribution and spatial interaction of innate and innate-like immune cells in the tumor microenvironment of periampullary adenocarcinoma. Methods: Multiplexed immunofluorescent imaging was performed on tissue microarrays with tumors from a consecutive cohort of 175 patients with resected periampullary adenocarcinoma. To obtain a detailed spatial analysis of immune cell infiltration, two multiplex immune panels including antibodies against CD3, NKp46, CD56, CD68, CD163 and CD1a, CD208, CD123, CD15, CD68 and pan-cytokeratin were applied. Results: The infiltration of natural killer (NK) and NK-like T (NKT) cells was lower in malignant compared to benign tissue. NKT cells were more abundant in intestinal type compared to pancreatobiliary type tumors, and were associated with more favorable clinicopathological features and a prolonged survival. The interaction of NKp46<sup>+</sup> NKT cells with macrophages was also associated with a prolonged survival. Conclusions: This study provides a comprehensive map of the innate immune landscape in periampullary adenocarcinoma. NK cells, and even more so NKT cells, are revealed to be central players in the local immune response in a clinically relevant context.</p>}},
  author       = {{Lundgren, Sebastian and Micke, Patrick and Elebro, Jacob and Heby, Margareta and Hrynchyk, Ina and Nodin, Björn and Leandersson, Karin and Mezheyeuski, Artur and Jirström, Karin}},
  issn         = {{1664-3224}},
  keywords     = {{dendritic cells; innate immunity; natural killer cells; natural killer T-cells; tumor microenvironment}},
  language     = {{eng}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Immunology}},
  title        = {{Topographical Distribution and Spatial Interactions of Innate and Semi-Innate Immune Cells in Pancreatic and Other Periampullary Adenocarcinoma}},
  url          = {{http://dx.doi.org/10.3389/fimmu.2020.558169}},
  doi          = {{10.3389/fimmu.2020.558169}},
  volume       = {{11}},
  year         = {{2020}},
}