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Cancer Immunology, Immunotherapy

, Volume 66, Issue 11, pp 1437–1447 | Cite as

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

  • 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. CarsonIII
Original Article

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.

Keywords

Myeloid-derived suppressor cells Breast cancer Chemotherapy Cytokines 

Abbreviations

CALGB

Cancer and Leukemia Group B

G-CSF

Granulocyte colony stimulating factor

G-MDSC

Granulocytic MDSC

HR

Hormone receptor

IRB

Institutional review board

M-MDSC

Monocytic MDSC

MDSC

Myeloid-derived suppressor cell(s)

NAC

Neo-adjuvant chemotherapy

PBMC

Peripheral blood mononuclear cell(s)

pCR

Pathologic complete response

RCB

Residual cancer burden

TNBC

Triple negative breast cancer

Notes

Acknowledgements

This work has been supported by the National Institutes of Health Grants 2P01CA095426-11, T32 GM068412 (to M. Duggan), K12 CA 133250 as well as the Ohio State Center for Clinical and Translational Science Richard P. and Marie R. Bremer Medical Research Fund and William H. Davis Endowment for Basic Medical Research Pilot Grant (UL1TR000090).

Compliance with ethical standards

Conflict of interest

The authors declare no commercial or financial conflict of interest.

Supplementary material

262_2017_2038_MOESM1_ESM.pdf (965 kb)
Supplementary material 1 (PDF 965 kb)

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Robert Wesolowski
    • 1
  • Megan C. Duggan
    • 2
  • Andrew Stiff
    • 2
  • Joseph Markowitz
    • 2
    • 6
  • Prashant Trikha
    • 2
  • Kala M. Levine
    • 2
  • Lynn Schoenfield
    • 3
  • Mahmoud Abdel-Rasoul
    • 4
  • Rachel Layman
    • 1
    • 7
  • Bhuvaneswari Ramaswamy
    • 1
  • Erin R. Macrae
    • 1
  • Maryam B. Lustberg
    • 1
  • Raquel E. Reinbolt
    • 1
  • Ewa Mrozek
    • 1
  • John C. Byrd
    • 2
  • Michael A. Caligiuri
    • 2
  • Thomas A. Mace
    • 2
  • William E. CarsonIII
    • 5
  1. 1.Department of Internal Medicine, Division of Medical OncologyThe Ohio State UniversityColumbusUSA
  2. 2.The Ohio State University Comprehensive Cancer CenterThe Ohio State UniversityColumbusUSA
  3. 3.Department of PathologyThe Ohio State UniversityColumbusUSA
  4. 4.Center for BiostatisticsThe Ohio State UniversityColumbusUSA
  5. 5.Division of Surgical Oncology, Department of SurgeryThe Ohio State UniversityColumbusUSA
  6. 6.Department of Cutaneous OncologyMoffitt Cancer CenterTampaUSA
  7. 7.Department of General OncologyThe University of Texas MD Anderson Cancer CenterHoustonUSA

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