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

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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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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

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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).

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Author notes

  1. Robert Wesolowski and Megan C. Duggan contributed equally to this paper.

Authors and Affiliations

  1. Department of Internal Medicine, Division of Medical Oncology, The Ohio State University, Starling Loving Hall, 320 W10th Ave, Columbus, OH, 43210, USA

    Robert Wesolowski, Rachel Layman, Bhuvaneswari Ramaswamy, Erin R. Macrae, Maryam B. Lustberg, Raquel E. Reinbolt & Ewa Mrozek

  2. The Ohio State University Comprehensive Cancer Center, The Ohio State University, 410 W 12th Avenue, Columbus, OH, 43210, USA

    Megan C. Duggan, Andrew Stiff, Joseph Markowitz, Prashant Trikha, Kala M. Levine, John C. Byrd, Michael A. Caligiuri & Thomas A. Mace

  3. Department of Pathology, The Ohio State University, 410 W 10th Ave, N337B Doan Hall, Columbus, OH, 43210-1267, USA

    Lynn Schoenfield

  4. Center for Biostatistics, The Ohio State University, 2012 Kenny Rd, Columbus, OH, 43221, USA

    Mahmoud Abdel-Rasoul

  5. Division of Surgical Oncology, Department of Surgery, The Ohio State University, 410 W 10th Ave, N911 Doan Hall, Columbus, OH, 43210-1267, USA

    William E. Carson III

  6. Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, 33612, USA

    Joseph Markowitz

  7. Department of General Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Rachel Layman

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  1. Robert Wesolowski
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  2. Megan C. Duggan
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Correspondence to William E. Carson III.

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Wesolowski, R., Duggan, M.C., Stiff, A. et al. Circulating myeloid-derived suppressor cells increase in patients undergoing neo-adjuvant chemotherapy for breast cancer. Cancer Immunol Immunother 66, 1437–1447 (2017). https://doi.org/10.1007/s00262-017-2038-3

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