Circulating myeloid-derived suppressor cells increase in patients undergoing neo-adjuvant chemotherapy for breast cancer
- 552 Downloads
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.
KeywordsMyeloid-derived suppressor cells Breast cancer Chemotherapy Cytokines
Cancer and Leukemia Group B
Granulocyte colony stimulating factor
Institutional review board
Myeloid-derived suppressor cell(s)
Peripheral blood mononuclear cell(s)
Pathologic complete response
Residual cancer burden
Triple negative breast cancer
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.
- 1.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) CrossRefGoogle Scholar
- 21.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 CrossRefPubMedPubMedCentralGoogle Scholar
- 24.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]Google Scholar
- 25.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 CrossRefPubMedGoogle Scholar
- 28.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] CrossRefGoogle Scholar
- 29.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 CrossRefPubMedPubMedCentralGoogle Scholar