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07.07.2017 | Original Article

Circulating myeloid-derived suppressor cells increase in patients undergoing neo-adjuvant chemotherapy for breast cancer

verfasst von: Robert Wesolowski, Megan C. Duggan, Andrew Stiff, Joseph Markowitz, Prashant Trikha, Kala M. Levine, Lynn Schoenfield, Mahmoud Abdel-Rasoul, Rachel Layman, Bhuvaneswari Ramaswamy, Erin R. Macrae, Maryam B. Lustberg, Raquel E. Reinbolt, Ewa Mrozek, John C. Byrd, Michael A. Caligiuri, Thomas A. Mace, William E. Carson III

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 11/2017

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Abstract

This study sought to evaluate whether myeloid-derived suppressor cells (MDSC) could be affected by chemotherapy and correlate with pathologic complete response (pCR) in breast cancer patients receiving neo-adjuvant chemotherapy. Peripheral blood levels of granulocytic (G-MDSC) and monocytic (M-MDSC) MDSC were measured by flow cytometry prior to cycle 1 and 2 of doxorubicin and cyclophosphamide and 1st and last administration of paclitaxel or paclitaxel/anti-HER2 therapy. Of 24 patients, 11, 6 and 7 patients were triple negative, HER2+ and hormone receptor+, respectively. 45.8% had pCR. Mean M-MDSC% were <1. Mean G-MDSC% and 95% confidence intervals were 0.88 (0.23–1.54), 5.07 (2.45–7.69), 9.32 (4.02–14.61) and 1.97 (0.53–3.41) at draws 1–4. The increase in G-MDSC by draw 3 was significant (p < 0.0001) in all breast cancer types. G-MDSC levels at the last draw were numerically lower in patients with pCR (1.15; 95% CI 0.14–2.16) versus patients with no pCR (2.71; 95% CI 0–5.47). There was no significant rise in G-MDSC from draw 1 to 3 in African American patients, and at draw 3 G-MDSC levels were significantly lower in African Americans versus Caucasians (p < 0.05). It was concluded that G-MDSC% increased during doxorubicin and cyclophosphamide therapy, but did not significantly differ between patients based on pathologic complete response.
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Literatur
1.
Zurück zum Zitat Wesolowski R, Duggan M, Stiff A et al. (2016) Abstract P4-09-18: Characterization of circulating myeloid derived suppressor cells and cytokines in patients undergoing neo-adjuvant chemotherapy for breast cancer. Cancer Res 76(4):P4-09-18. doi:10.1158/1538-7445.SABCS15-P4-09-18 (Abstract P4-09-18) CrossRef Wesolowski R, Duggan M, Stiff A et al. (2016) Abstract P4-09-18: Characterization of circulating myeloid derived suppressor cells and cytokines in patients undergoing neo-adjuvant chemotherapy for breast cancer. Cancer Res 76(4):P4-09-18. doi:10.​1158/​1538-7445.​SABCS15-P4-09-18 (Abstract P4-09-18) CrossRef
2.
6.
Zurück zum Zitat Markowitz J, Brooks TR, Duggan MC et al (2015) Patients with pancreatic adenocarcinoma exhibit elevated levels of myeloid-derived suppressor cells upon progression of disease. Cancer Immunol Immunother 64:149–159. doi:10.1007/s00262-014-1618-8 CrossRefPubMed Markowitz J, Brooks TR, Duggan MC et al (2015) Patients with pancreatic adenocarcinoma exhibit elevated levels of myeloid-derived suppressor cells upon progression of disease. Cancer Immunol Immunother 64:149–159. doi:10.​1007/​s00262-014-1618-8 CrossRefPubMed
8.
11.
Zurück zum Zitat Bronte V, Apolloni E, Cabrelle A et al (2000) Identification of a CD11b(+)/Gr-1(+)/CD31(+) myeloid progenitor capable of activating or suppressing CD8(+) T cells. Blood 96:3838–3846PubMedPubMedCentral Bronte V, Apolloni E, Cabrelle A et al (2000) Identification of a CD11b(+)/Gr-1(+)/CD31(+) myeloid progenitor capable of activating or suppressing CD8(+) T cells. Blood 96:3838–3846PubMedPubMedCentral
13.
Zurück zum Zitat Li H, Han Y, Guo Q et al (2009) Cancer-expanded myeloid-derived suppressor cells induce anergy of NK cells through membrane-bound TGF-beta 1. J Immunol 182:240–249CrossRefPubMed Li H, Han Y, Guo Q et al (2009) Cancer-expanded myeloid-derived suppressor cells induce anergy of NK cells through membrane-bound TGF-beta 1. J Immunol 182:240–249CrossRefPubMed
16.
Zurück zum Zitat Scholl SM, Pierga JY, Asselain B et al (1995) Breast tumour response to primary chemotherapy predicts local and distant control as well as survival. Eur J Cancer 31A:1969–1975CrossRefPubMed Scholl SM, Pierga JY, Asselain B et al (1995) Breast tumour response to primary chemotherapy predicts local and distant control as well as survival. Eur J Cancer 31A:1969–1975CrossRefPubMed
18.
Zurück zum Zitat Baselga J, Bradbury I, Eidtmann H et al (2012) Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet (London, England) 379:633–640. doi:10.1016/S0140-6736(11)61847-3 CrossRef Baselga J, Bradbury I, Eidtmann H et al (2012) Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet (London, England) 379:633–640. doi:10.​1016/​S0140-6736(11)61847-3 CrossRef
19.
Zurück zum Zitat Lesinski GB, Kondadasula SV, Crespin T et al (2004) Multiparametric flow cytometric analysis of inter-patient variation in STAT1 phosphorylation following interferon Alfa immunotherapy. J Natl Cancer Inst 96:1331–1342. doi:10.1093/jnci/djh252 CrossRefPubMed Lesinski GB, Kondadasula SV, Crespin T et al (2004) Multiparametric flow cytometric analysis of inter-patient variation in STAT1 phosphorylation following interferon Alfa immunotherapy. J Natl Cancer Inst 96:1331–1342. doi:10.​1093/​jnci/​djh252 CrossRefPubMed
21.
Zurück zum Zitat Mundy-Bosse BL, Young GS, Bauer T et al (2011) Distinct myeloid suppressor cell subsets correlate with plasma IL-6 and IL-10 and reduced interferon-alpha signaling in CD4+ T cells from patients with GI malignancy. Cancer Immunol Immunother 60:1269–1279. doi:10.1007/s00262-011-1029-z CrossRefPubMedPubMedCentral Mundy-Bosse BL, Young GS, Bauer T et al (2011) Distinct myeloid suppressor cell subsets correlate with plasma IL-6 and IL-10 and reduced interferon-alpha signaling in CD4+ T cells from patients with GI malignancy. Cancer Immunol Immunother 60:1269–1279. doi:10.​1007/​s00262-011-1029-z CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Wesolowski R, Budd GT (2009) Neoadjuvant therapy for breast cancer: assessing treatment progress and managing poor responders. Curr Oncol Rep 11:37–44CrossRefPubMed Wesolowski R, Budd GT (2009) Neoadjuvant therapy for breast cancer: assessing treatment progress and managing poor responders. Curr Oncol Rep 11:37–44CrossRefPubMed
24.
Zurück zum Zitat Sikov WM, Berry DA, Perou CM et al (2015) Event-free and overall survival following neoadjuvant weekly paclitaxel and dose-dense AC ± carboplatin and/or bevacizumab in triple-negative breast cancer: outcomes from CALGB 40603 (Alliance). In: 2015 San Antonio Breast Cancer Symp. [Abstract] Sikov WM, Berry DA, Perou CM et al (2015) Event-free and overall survival following neoadjuvant weekly paclitaxel and dose-dense AC ± carboplatin and/or bevacizumab in triple-negative breast cancer: outcomes from CALGB 40603 (Alliance). In: 2015 San Antonio Breast Cancer Symp. [Abstract]
25.
Zurück zum Zitat Diaz-Montero CM, Salem ML, Nishimura MI et al (2009) Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother 58:49–59. doi:10.1007/s00262-008-0523-4 CrossRefPubMed Diaz-Montero CM, Salem ML, Nishimura MI et al (2009) Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother 58:49–59. doi:10.​1007/​s00262-008-0523-4 CrossRefPubMed
26.
Zurück zum Zitat Sinha P, Clements VK, Bunt SK et al (2007) Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response. J Immunol 179:977–983CrossRefPubMed Sinha P, Clements VK, Bunt SK et al (2007) Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response. J Immunol 179:977–983CrossRefPubMed
27.
Zurück zum Zitat Almand B, Resser JR, Lindman B et al (2000) Clinical significance of defective dendritic cell differentiation in cancer. Clin Cancer Res 6:1755–1766PubMed Almand B, Resser JR, Lindman B et al (2000) Clinical significance of defective dendritic cell differentiation in cancer. Clin Cancer Res 6:1755–1766PubMed
28.
Zurück zum Zitat Cole S, Montero A, Garret-Mayer E et al (2009) Elevated circulating myeloid derived suppressor cells (MDSC) are associated with inferior overall survival (OS) and correlate with circulating tumor cells (CTC) in patients with metastatic breast cancer. Cancer Res 69:4135. doi:10.1158/0008-5472.SABCS-09-4135 [Abstract] CrossRef Cole S, Montero A, Garret-Mayer E et al (2009) Elevated circulating myeloid derived suppressor cells (MDSC) are associated with inferior overall survival (OS) and correlate with circulating tumor cells (CTC) in patients with metastatic breast cancer. Cancer Res 69:4135. doi:10.​1158/​0008-5472.​SABCS-09-4135 [Abstract] CrossRef
29.
Zurück zum Zitat Gabitass RF, Annels NE, Stocken DD et al (2011) Elevated myeloid-derived suppressor cells in pancreatic, esophageal and gastric cancer are an independent prognostic factor and are associated with significant elevation of the Th2 cytokine interleukin-13. Cancer Immunol Immunother 60:1419–1430. doi:10.1007/s00262-011-1028-0 CrossRefPubMedPubMedCentral Gabitass RF, Annels NE, Stocken DD et al (2011) Elevated myeloid-derived suppressor cells in pancreatic, esophageal and gastric cancer are an independent prognostic factor and are associated with significant elevation of the Th2 cytokine interleukin-13. Cancer Immunol Immunother 60:1419–1430. doi:10.​1007/​s00262-011-1028-0 CrossRefPubMedPubMedCentral
Metadaten
Titel
Circulating myeloid-derived suppressor cells increase in patients undergoing neo-adjuvant chemotherapy for breast cancer
verfasst von
Robert Wesolowski
Megan C. Duggan
Andrew Stiff
Joseph Markowitz
Prashant Trikha
Kala M. Levine
Lynn Schoenfield
Mahmoud Abdel-Rasoul
Rachel Layman
Bhuvaneswari Ramaswamy
Erin R. Macrae
Maryam B. Lustberg
Raquel E. Reinbolt
Ewa Mrozek
John C. Byrd
Michael A. Caligiuri
Thomas A. Mace
William E. Carson III
Publikationsdatum
07.07.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Immunology, Immunotherapy / Ausgabe 11/2017
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-017-2038-3

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