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Published in: Breast Cancer Research 1/2021

01-12-2021 | Breast Cancer | Research article

Circulating immune cell populations related to primary breast cancer, surgical removal, and radiotherapy revealed by flow cytometry analysis

Authors: Sarah Cattin, Benoît Fellay, Antonello Calderoni, Alexandre Christinat, Laura Negretti, Maira Biggiogero, Alberto Badellino, Anne-Lise Schneider, Pelagia Tsoutsou, Alessandra Franzetti Pellanda, Curzio Rüegg

Published in: Breast Cancer Research | Issue 1/2021

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Abstract

Background

Advanced breast cancer (BC) impact immune cells in the blood but whether such effects may reflect the presence of early BC and its therapeutic management remains elusive.

Methods

To address this question, we used multiparametric flow cytometry to analyze circulating leukocytes in patients with early BC (n = 13) at the time of diagnosis, after surgery, and after adjuvant radiotherapy, compared to healthy individuals. Data were analyzed using a minimally supervised approach based on FlowSOM algorithm and validated manually.

Results

At the time of diagnosis, BC patients have an increased frequency of CD117+CD11b+ granulocytes, which was significantly reduced after tumor removal. Adjuvant radiotherapy increased the frequency of CD45RO+ memory CD4+ T cells and CD4+ regulatory T cells. FlowSOM algorithm analysis revealed several unanticipated populations, including cells negative for all markers tested, CD11b+CD15low, CD3+CD4CD8, CD3+CD4+CD8+, and CD3+CD8+CD127+CD45RO+ cells, associated with BC or radiotherapy.

Conclusions

This study revealed changes in blood leukocytes associated with primary BC, surgical removal, and adjuvant radiotherapy. Specifically, it identified increased levels of CD117+ granulocytes, memory, and regulatory CD4+ T cells as potential biomarkers of BC and radiotherapy, respectively. Importantly, the study demonstrates the value of unsupervised analysis of complex flow cytometry data to unravel new cell populations of potential clinical relevance.
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Literature
10.
go back to reference Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347(16):1233–41. https://doi.org/10.1056/NEJMoa022152.CrossRefPubMed Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002;347(16):1233–41. https://​doi.​org/​10.​1056/​NEJMoa022152.CrossRefPubMed
16.
go back to reference Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10 801 women in 17 randomised trials. Lancet. 2011;378(9804):1707–16. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10 801 women in 17 randomised trials. Lancet. 2011;378(9804):1707–16.
19.
go back to reference Drooger JC, Hooning MJ, Seynaeve CM, Baaijens MHA, Obdeijn IM, Sleijfer S, et al. Diagnostic and therapeutic ionizing radiation and the risk of a first and second primary breast cancer, with special attention for BRCA1 and BRCA2 mutation carriers: A critical review of the literature. Cancer Treatment Rev. 2015;41(2):187–96. https://doi.org/10.1016/j.ctrv.2014.12.002.CrossRef Drooger JC, Hooning MJ, Seynaeve CM, Baaijens MHA, Obdeijn IM, Sleijfer S, et al. Diagnostic and therapeutic ionizing radiation and the risk of a first and second primary breast cancer, with special attention for BRCA1 and BRCA2 mutation carriers: A critical review of the literature. Cancer Treatment Rev. 2015;41(2):187–96. https://​doi.​org/​10.​1016/​j.​ctrv.​2014.​12.​002.CrossRef
27.
go back to reference Buono G, Gerratana L, Bulfoni M, Provinciali N, Basile D, Giuliano M, et al. Circulating tumor DNA analysis in breast cancer: is it ready for prime-time? Cancer Treatment Rev. 2019;73:73–83.CrossRef Buono G, Gerratana L, Bulfoni M, Provinciali N, Basile D, Giuliano M, et al. Circulating tumor DNA analysis in breast cancer: is it ready for prime-time? Cancer Treatment Rev. 2019;73:73–83.CrossRef
35.
go back to reference Schmittgen TD, Lee EJ, Jiang J, Sarkar A, Yang L, Elton TS and Chen C. Real-time PCR quantification of precursor and mature microRNA. Methods. 2008;44(1):31–8. Schmittgen TD, Lee EJ, Jiang J, Sarkar A, Yang L, Elton TS and Chen C. Real-time PCR quantification of precursor and mature microRNA. Methods. 2008;44(1):31–8.
36.
go back to reference Broxmeyer HE, Maze R, Miyazawa K, Carow C, Hendrie PC, Cooper S, et al. The kit receptor and its ligand, steel factor, as regulators of hemopoiesis. Cancer Cells. 1991;3(12):480–7.PubMed Broxmeyer HE, Maze R, Miyazawa K, Carow C, Hendrie PC, Cooper S, et al. The kit receptor and its ligand, steel factor, as regulators of hemopoiesis. Cancer Cells. 1991;3(12):480–7.PubMed
37.
go back to reference D’Arena G, Musto P, Cascavilla N, Carotenuto M. Thy-1 (CDw90) and c-kit receptor (CD117) expression on CD34+ hematopoietic progenitor cells: a five dimensional flow cytometric study. Haematologica. 1998;83(7):587–92.PubMed D’Arena G, Musto P, Cascavilla N, Carotenuto M. Thy-1 (CDw90) and c-kit receptor (CD117) expression on CD34+ hematopoietic progenitor cells: a five dimensional flow cytometric study. Haematologica. 1998;83(7):587–92.PubMed
39.
go back to reference Jatoi I, Benson JR, Kunkler I. Hypothesis: can the abscopal effect explain the impact of adjuvant radiotherapy on breast cancer mortality? NPJ Breast Cancer. 2018;4(1):8.CrossRef Jatoi I, Benson JR, Kunkler I. Hypothesis: can the abscopal effect explain the impact of adjuvant radiotherapy on breast cancer mortality? NPJ Breast Cancer. 2018;4(1):8.CrossRef
42.
go back to reference Zielinski CC, Müller C, Kubista E, Staffen A, Eibl MM. Effects of adjuvant chemotherapy on specific and non-specific immune mechanisms. Acta Med Austriaca. 1990;17(1):11–4.PubMed Zielinski CC, Müller C, Kubista E, Staffen A, Eibl MM. Effects of adjuvant chemotherapy on specific and non-specific immune mechanisms. Acta Med Austriaca. 1990;17(1):11–4.PubMed
52.
go back to reference Johnke RM, Edwards JM, Kovacs CJ, Evans MJ, Daly BM, Karlsson UL, et al. Response of T lymphocyte populations in prostate cancer patients undergoing radiotherapy: influence of neoajuvant total androgen suppression. Anticancer Res. 2005;25(4):3159–66.PubMed Johnke RM, Edwards JM, Kovacs CJ, Evans MJ, Daly BM, Karlsson UL, et al. Response of T lymphocyte populations in prostate cancer patients undergoing radiotherapy: influence of neoajuvant total androgen suppression. Anticancer Res. 2005;25(4):3159–66.PubMed
53.
go back to reference Lissoni P, Brivio F, Fumagalli L, Messina G, Meregalli S, Porro G, et al. Effects of the conventional antitumor therapies surgery, chemotherapy, radiotherapy and immunotherapy on regulatory T lymphocytes in cancer patients. Anticancer Res. 2009;29(5):1847–52.PubMed Lissoni P, Brivio F, Fumagalli L, Messina G, Meregalli S, Porro G, et al. Effects of the conventional antitumor therapies surgery, chemotherapy, radiotherapy and immunotherapy on regulatory T lymphocytes in cancer patients. Anticancer Res. 2009;29(5):1847–52.PubMed
Metadata
Title
Circulating immune cell populations related to primary breast cancer, surgical removal, and radiotherapy revealed by flow cytometry analysis
Authors
Sarah Cattin
Benoît Fellay
Antonello Calderoni
Alexandre Christinat
Laura Negretti
Maira Biggiogero
Alberto Badellino
Anne-Lise Schneider
Pelagia Tsoutsou
Alessandra Franzetti Pellanda
Curzio Rüegg
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2021
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-021-01441-8

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