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AIRE is expressed in breast cancer TANs and TAMs to regulate the extrinsic apoptotic pathway and inflammation

Källberg, Eva LU ; Mehmeti-Ajradini, Meliha LU ; Gunnarsdottir, Frida Björk LU ; Göransson, Marcus ; Bergenfelz, Caroline LU orcid ; Fredriksson, Roni Allaoui ; Hagerling, Catharina LU ; Johansson, Martin E LU ; Welinder, Charlotte LU and Jirström, Karin LU orcid , et al. (2024) In Journal of Leukocyte Biology 115(4). p.664-678
Abstract

Autoimmune regulator (AIRE) is a transcriptional regulator expressed in the thymus and necessary for maintaining immunological self-tolerance. Extra-thymic AIRE expression is rare and a role for AIRE in tumor-associated innate immune cells has not yet been established. In this study we show that AIRE is expressed in human pro-tumor neutrophils. In breast cancer, AIRE was primarily located to tumor associated neutrophils (TANs), and to a lesser extent to tumor associated macrophages (TAMs) and tumor cells. Expression of AIRE in TAN/TAMs, but not in cancer cells, was associated with an adverse prognosis. We show that the functional role for AIRE in neutrophils and macrophages is to regulate expression of immune mediators and the extrinsic... (More)

Autoimmune regulator (AIRE) is a transcriptional regulator expressed in the thymus and necessary for maintaining immunological self-tolerance. Extra-thymic AIRE expression is rare and a role for AIRE in tumor-associated innate immune cells has not yet been established. In this study we show that AIRE is expressed in human pro-tumor neutrophils. In breast cancer, AIRE was primarily located to tumor associated neutrophils (TANs), and to a lesser extent to tumor associated macrophages (TAMs) and tumor cells. Expression of AIRE in TAN/TAMs, but not in cancer cells, was associated with an adverse prognosis. We show that the functional role for AIRE in neutrophils and macrophages is to regulate expression of immune mediators and the extrinsic apoptotic pathway involving the Fas/TNFR death receptors and Cathepsin G. We here propose that the role for AIRE in TAN/TAMs in breast tumors is to regulate cell death and inflammation, thus promoting tumor progression.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Leukocyte Biology
volume
115
issue
4
article number
qiad152
pages
664 - 678
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:38060995
  • scopus:85189291270
ISSN
1938-3673
DOI
10.1093/jleuko/qiad152
language
English
LU publication?
yes
id
d073c09b-b796-4f32-9ef7-d7f806446ad5
date added to LUP
2023-12-08 14:18:37
date last changed
2024-12-21 16:18:46
@article{d073c09b-b796-4f32-9ef7-d7f806446ad5,
  abstract     = {{<p>Autoimmune regulator (AIRE) is a transcriptional regulator expressed in the thymus and necessary for maintaining immunological self-tolerance. Extra-thymic AIRE expression is rare and a role for AIRE in tumor-associated innate immune cells has not yet been established. In this study we show that AIRE is expressed in human pro-tumor neutrophils. In breast cancer, AIRE was primarily located to tumor associated neutrophils (TANs), and to a lesser extent to tumor associated macrophages (TAMs) and tumor cells. Expression of AIRE in TAN/TAMs, but not in cancer cells, was associated with an adverse prognosis. We show that the functional role for AIRE in neutrophils and macrophages is to regulate expression of immune mediators and the extrinsic apoptotic pathway involving the Fas/TNFR death receptors and Cathepsin G. We here propose that the role for AIRE in TAN/TAMs in breast tumors is to regulate cell death and inflammation, thus promoting tumor progression.</p>}},
  author       = {{Källberg, Eva and Mehmeti-Ajradini, Meliha and Gunnarsdottir, Frida Björk and Göransson, Marcus and Bergenfelz, Caroline and Fredriksson, Roni Allaoui and Hagerling, Catharina and Johansson, Martin E and Welinder, Charlotte and Jirström, Karin and Leandersson, Karin}},
  issn         = {{1938-3673}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{664--678}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Journal of Leukocyte Biology}},
  title        = {{AIRE is expressed in breast cancer TANs and TAMs to regulate the extrinsic apoptotic pathway and inflammation}},
  url          = {{http://dx.doi.org/10.1093/jleuko/qiad152}},
  doi          = {{10.1093/jleuko/qiad152}},
  volume       = {{115}},
  year         = {{2024}},
}