Unbiased high-dimensional flow cytometry identified NK and DC immune cell signature in Luminal A-type and triple negative breast cancer

ABSTRACTBreast cancer is the most common malignancy in women worldwide and a highly heterogeneous disease. Four different subtypes are described that differ in the expression of hormone receptors as well as the growth factor receptor HER2. Treatment modalities and survival rate depend on the subtype...

Full description

Bibliographic Details
Main Authors: Lukas Heger, Gordon F. Heidkamp, Lukas Amon, Falk Nimmerjahn, Tobias Bäuerle, Andreas Maier, Ramona Erber, Arndt Hartmann, Carolin C. Hack, Matthias Ruebner, Hanna Huebner, Peter Fasching, Matthias W. Beckmann, Diana Dudziak
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:OncoImmunology
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/2162402X.2023.2296713
_version_ 1797382693267177472
author Lukas Heger
Gordon F. Heidkamp
Lukas Amon
Falk Nimmerjahn
Tobias Bäuerle
Andreas Maier
Ramona Erber
Arndt Hartmann
Carolin C. Hack
Matthias Ruebner
Hanna Huebner
Peter Fasching
Matthias W. Beckmann
Diana Dudziak
author_facet Lukas Heger
Gordon F. Heidkamp
Lukas Amon
Falk Nimmerjahn
Tobias Bäuerle
Andreas Maier
Ramona Erber
Arndt Hartmann
Carolin C. Hack
Matthias Ruebner
Hanna Huebner
Peter Fasching
Matthias W. Beckmann
Diana Dudziak
author_sort Lukas Heger
collection DOAJ
description ABSTRACTBreast cancer is the most common malignancy in women worldwide and a highly heterogeneous disease. Four different subtypes are described that differ in the expression of hormone receptors as well as the growth factor receptor HER2. Treatment modalities and survival rate depend on the subtype of breast cancer. However, it is still not clear which patients benefit from immunotherapeutic approaches such as checkpoint blockade. Thus, we aimed to decipher the immune cell signature of the different breast cancer subtypes based on high-dimensional flow cytometry followed by unbiased approaches. Here, we show that the frequency of NK cells is reduced in Luminal A and B as well as triple negative breast cancer and that the phenotype of residual NK cells is changed toward regulatory CD11b−CD16− NK cells. Further, we found higher frequencies of PD-1+ CD4+ and CD8+ T cells in triple negative breast cancer. Moreover, while Luminal A-type breast cancer was enriched for CD14+ cDC2 (named type 3 DC (DC3)), CD14− cDC2 (named DC2) were more frequent in triple negative breast cancer. In contrast, HER2-enriched breast cancer did not show major alterations in the composition of the immune cell compartment in the tumor microenvironment. These findings suggest that patients with Luminal A- and B-type as well as triple negative breast cancer might benefit from immunotherapeutic approaches targeting NK cells.
first_indexed 2024-03-08T21:09:13Z
format Article
id doaj.art-2fea48d7018642c3a2bf91299e025a26
institution Directory Open Access Journal
issn 2162-402X
language English
last_indexed 2024-03-08T21:09:13Z
publishDate 2024-12-01
publisher Taylor & Francis Group
record_format Article
series OncoImmunology
spelling doaj.art-2fea48d7018642c3a2bf91299e025a262023-12-22T08:38:56ZengTaylor & Francis GroupOncoImmunology2162-402X2024-12-0113110.1080/2162402X.2023.2296713Unbiased high-dimensional flow cytometry identified NK and DC immune cell signature in Luminal A-type and triple negative breast cancerLukas Heger0Gordon F. Heidkamp1Lukas Amon2Falk Nimmerjahn3Tobias Bäuerle4Andreas Maier5Ramona Erber6Arndt Hartmann7Carolin C. Hack8Matthias Ruebner9Hanna Huebner10Peter Fasching11Matthias W. Beckmann12Diana Dudziak13Department of Dermatology, Laboratory of Dendritic Cell Biology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyDepartment of Dermatology, Laboratory of Dendritic Cell Biology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyDepartment of Dermatology, Laboratory of Dendritic Cell Biology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyChair of Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyInstitute of Radiology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyChair of Computer Science 5 (Pattern Recognition), Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyInstitute of Pathology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyInstitute of Pathology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyComprehensive Cancer Center Erlangen-European Metropolitan Area of Nuremberg (CCC ER-EMN), Erlangen, GermanyComprehensive Cancer Center Erlangen-European Metropolitan Area of Nuremberg (CCC ER-EMN), Erlangen, GermanyComprehensive Cancer Center Erlangen-European Metropolitan Area of Nuremberg (CCC ER-EMN), Erlangen, GermanyComprehensive Cancer Center Erlangen-European Metropolitan Area of Nuremberg (CCC ER-EMN), Erlangen, GermanyComprehensive Cancer Center Erlangen-European Metropolitan Area of Nuremberg (CCC ER-EMN), Erlangen, GermanyDepartment of Dermatology, Laboratory of Dendritic Cell Biology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyABSTRACTBreast cancer is the most common malignancy in women worldwide and a highly heterogeneous disease. Four different subtypes are described that differ in the expression of hormone receptors as well as the growth factor receptor HER2. Treatment modalities and survival rate depend on the subtype of breast cancer. However, it is still not clear which patients benefit from immunotherapeutic approaches such as checkpoint blockade. Thus, we aimed to decipher the immune cell signature of the different breast cancer subtypes based on high-dimensional flow cytometry followed by unbiased approaches. Here, we show that the frequency of NK cells is reduced in Luminal A and B as well as triple negative breast cancer and that the phenotype of residual NK cells is changed toward regulatory CD11b−CD16− NK cells. Further, we found higher frequencies of PD-1+ CD4+ and CD8+ T cells in triple negative breast cancer. Moreover, while Luminal A-type breast cancer was enriched for CD14+ cDC2 (named type 3 DC (DC3)), CD14− cDC2 (named DC2) were more frequent in triple negative breast cancer. In contrast, HER2-enriched breast cancer did not show major alterations in the composition of the immune cell compartment in the tumor microenvironment. These findings suggest that patients with Luminal A- and B-type as well as triple negative breast cancer might benefit from immunotherapeutic approaches targeting NK cells.https://www.tandfonline.com/doi/10.1080/2162402X.2023.2296713Breast cancerimmune cell signatureNK cellsPD-1tumor microenvironment
spellingShingle Lukas Heger
Gordon F. Heidkamp
Lukas Amon
Falk Nimmerjahn
Tobias Bäuerle
Andreas Maier
Ramona Erber
Arndt Hartmann
Carolin C. Hack
Matthias Ruebner
Hanna Huebner
Peter Fasching
Matthias W. Beckmann
Diana Dudziak
Unbiased high-dimensional flow cytometry identified NK and DC immune cell signature in Luminal A-type and triple negative breast cancer
OncoImmunology
Breast cancer
immune cell signature
NK cells
PD-1
tumor microenvironment
title Unbiased high-dimensional flow cytometry identified NK and DC immune cell signature in Luminal A-type and triple negative breast cancer
title_full Unbiased high-dimensional flow cytometry identified NK and DC immune cell signature in Luminal A-type and triple negative breast cancer
title_fullStr Unbiased high-dimensional flow cytometry identified NK and DC immune cell signature in Luminal A-type and triple negative breast cancer
title_full_unstemmed Unbiased high-dimensional flow cytometry identified NK and DC immune cell signature in Luminal A-type and triple negative breast cancer
title_short Unbiased high-dimensional flow cytometry identified NK and DC immune cell signature in Luminal A-type and triple negative breast cancer
title_sort unbiased high dimensional flow cytometry identified nk and dc immune cell signature in luminal a type and triple negative breast cancer
topic Breast cancer
immune cell signature
NK cells
PD-1
tumor microenvironment
url https://www.tandfonline.com/doi/10.1080/2162402X.2023.2296713
work_keys_str_mv AT lukasheger unbiasedhighdimensionalflowcytometryidentifiednkanddcimmunecellsignatureinluminalatypeandtriplenegativebreastcancer
AT gordonfheidkamp unbiasedhighdimensionalflowcytometryidentifiednkanddcimmunecellsignatureinluminalatypeandtriplenegativebreastcancer
AT lukasamon unbiasedhighdimensionalflowcytometryidentifiednkanddcimmunecellsignatureinluminalatypeandtriplenegativebreastcancer
AT falknimmerjahn unbiasedhighdimensionalflowcytometryidentifiednkanddcimmunecellsignatureinluminalatypeandtriplenegativebreastcancer
AT tobiasbauerle unbiasedhighdimensionalflowcytometryidentifiednkanddcimmunecellsignatureinluminalatypeandtriplenegativebreastcancer
AT andreasmaier unbiasedhighdimensionalflowcytometryidentifiednkanddcimmunecellsignatureinluminalatypeandtriplenegativebreastcancer
AT ramonaerber unbiasedhighdimensionalflowcytometryidentifiednkanddcimmunecellsignatureinluminalatypeandtriplenegativebreastcancer
AT arndthartmann unbiasedhighdimensionalflowcytometryidentifiednkanddcimmunecellsignatureinluminalatypeandtriplenegativebreastcancer
AT carolinchack unbiasedhighdimensionalflowcytometryidentifiednkanddcimmunecellsignatureinluminalatypeandtriplenegativebreastcancer
AT matthiasruebner unbiasedhighdimensionalflowcytometryidentifiednkanddcimmunecellsignatureinluminalatypeandtriplenegativebreastcancer
AT hannahuebner unbiasedhighdimensionalflowcytometryidentifiednkanddcimmunecellsignatureinluminalatypeandtriplenegativebreastcancer
AT peterfasching unbiasedhighdimensionalflowcytometryidentifiednkanddcimmunecellsignatureinluminalatypeandtriplenegativebreastcancer
AT matthiaswbeckmann unbiasedhighdimensionalflowcytometryidentifiednkanddcimmunecellsignatureinluminalatypeandtriplenegativebreastcancer
AT dianadudziak unbiasedhighdimensionalflowcytometryidentifiednkanddcimmunecellsignatureinluminalatypeandtriplenegativebreastcancer