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The significant increase and dynamic changes of the myeloid-derived suppressor cells percentage with chemotherapy in advanced NSCLC patients

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Abstract

Purpose

To investigate the correlations between myeloid-derived suppressor cells (MDSCs) in the peripheral blood and cancer stage, immune function, and chemotherapy.

Methods

Percentages of MDSCs (CD11b+CD14−CD33+ cells) and lymphocyte subsets in peripheral blood mononuclear cells (PBMCs) of 94 patients with Non-small cell lung cancer (NSCLC) who were treated naïve and 30 healthy individuals were measured. Changes of the MDSCs percentage were further detected in patients with advanced NSCLC treated with systemic chemotherapy. Finally, coculture with CD8+ cells was developed to determine effect of MDSCs on IFN-γ secretion of T lymphocytes.

Results

MDSCs percentage of 94 patients with NSCLC was significantly higher than that of 30 healthy subjects (P < 0.05), the percentages were increased with tumor progression, in patients with stage III and IV percentages were significantly higher than those in stage I and II patients (P = 0.013). The MDSCs percentage was negatively related to percentage of CD8+ cells in the peripheral blood (r = −0.354, n = 38, P = 0.029), and when they were cocultured, IFN-γ secretion of CD8+ cells was significantly decreased (P < 0.05). In 20 patients with advanced NSCLC who received systemic chemotherapy, nine partial remission (PR) cases got MDSCs percentage significantly decreased (P < 0.001), three stable disease (SD) cases remained invariable (P = 0.307) and eight progressive disease (PD) cases got significantly increased (P = 0.024).

Conclusion

The percentage of MDSCs in the patients was significantly higher than that of the healthy control subjects and it increased with tumor progression partially by inhibiting the CD8+ cell function. The dynamic changes of MDSCs percentage reflected the efficacy of systemic chemotherapy.

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References

  1. Gonda TA, Tu S, Wang TC. Chronic inflammation, the tumor microenvironment and carcinogenesis. Cell Cycle. 2009;8:2005–13.

    Article  CAS  PubMed  Google Scholar 

  2. Zamarron BF, Chen W. Dual roles of immune cells and their factors in cancer development and progression. Int J Biol Sci. 2011;7:651–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Haile LA, Greten TF, Korangy F. Immune suppression: the hallmark of myeloid derived suppressor cells. Immunol Invest. 2012;41:581–94.

    Article  CAS  PubMed  Google Scholar 

  4. Qu P, Boelte KC, Lin PC. Negative regulation of myeloid-derived suppressor cells in cancer. Immunol Invest. 2012;41:562–80.

    Article  PubMed  Google Scholar 

  5. Gabrilovich DI, Bronte V, Chen SH, Colombo MP, Ochoa A, Ostrand-Rosenberg S, et al. The terminology issue for myeloid-derived suppressor cells. Cancer Res. 2007;67:425–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Lindau D, Gielen P, Kroesen M, Wesseling P, Adema GJ. The immunosuppressive tumour network: myeloid-derived suppressor cells, regulatory T cells and natural killer T cells. Immunology. 2013;138:105–15.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Ostrand-Rosenberg S, Sinha P, Beury DW, Clements VK. Cross-talk between myeloid-derived suppressor cells (MDSC), macrophages, and dendritic cells enhances tumor-induced immune suppression. Semin Cancer Biol. 2012;22:275–81.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Talmadge JE. Pathways mediating the expansion and immunosuppressive activity of myeloid-derived suppressor cells and their relevance to cancer therapy. Clin Cancer Res. 2007;13:5243–8.

    Article  CAS  PubMed  Google Scholar 

  9. Youn JI, Nagaraj S, Collazo M, Gabrilovich DI. Subsets of myeloid-derived suppressor cells in tumor-bearing mice. J Immunol. 2008;181:5791–802.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Chandra D, Jahangir A, Quispe-Tintaya W, Einstein MH, Gravekamp C. Myeloid-derived suppressor cells have a central role in attenuated Listeria monocytogenes-based immunotherapy against metastatic breast cancer in young and old mice. Br J Cancer. 2013;108:2281–90.

    Article  CAS  PubMed  Google Scholar 

  11. Filipazzi P, Huber V, Rivoltini L. Phenotype, function and clinical implications of myeloid-derived suppressor cells in cancer patients. Cancer Immunol Immunother. 2012;61:255–63.

    Article  CAS  PubMed  Google Scholar 

  12. Diaz-Montero CM, Salem ML, Nishimura MI, Garrett-Mayer E, Cole DJ, Montero AJ. Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother. 2009;58:49–59.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Sun HL, Zhou X, Xue YF, Wang K, Shen YF, Mao JJ, et al. Increased frequency and clinical significance of myeloid-derived suppressor cells in human colorectal carcinoma. World J Gastroenterol. 2012;18:3303–9.

    PubMed Central  PubMed  Google Scholar 

  14. Zhang B, Wang Z, Wu L, Zhang M, Li W, Ding J, et al. Circulating and tumor-infiltrating myeloid-derived suppressor cells in patients with colorectal carcinoma. PLoS ONE. 2013;8:e57114.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Liu CY, Wang YM, Wang CL, Feng PH, Ko HW, Liu YH, et al. Population alterations of L-arginase- and inducible nitric oxide synthase-expressed CD11b+/CD14−/CD15+/CD33+ myeloid-derived suppressor cells and CD8+ T lymphocytes in patients with advanced-stage non-small cell lung cancer. J Cancer Res Clin Oncol. 2010;136:35–45.

    Article  CAS  PubMed  Google Scholar 

  16. Mirza N, Fishman M, Fricke I, Dunn M, Neuger AM, Frost TJ, et al. All-trans-retinoic acid improves differentiation of myeloid cells and immune response in cancer patients. Cancer Res. 2006;66:9299–307.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Ko JS, Rayman P, Ireland J, Swaidani S, Li G, Bunting KD, et al. Direct and differential suppression of myeloid-derived suppressor cell subsets by sunitinib is compartmentally constrained. Cancer Res. 2010;70:3526–36.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Ko JS, Zea AH, Rini BI, Ireland JL, Elson P, Cohen P, et al. Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin Cancer Res. 2009;15:2148–57.

    Article  CAS  PubMed  Google Scholar 

  19. Xin H, Zhang C, Herrmann A, Du Y, Figlin R, Yu H. Sunitinib inhibition of Stat3 induces renal cell carcinoma tumor cell apoptosis and reduces immunosuppressive cells. Cancer Res. 2009;69:2506–13.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Suzuki E, Kapoor V, Jassar AS, Kaiser LR, Albelda SM. Gemcitabine selectively eliminates splenic Gr-1+/CD11b+ myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity. Clin Cancer Res. 2005;11:6713–21.

    Article  CAS  PubMed  Google Scholar 

  21. Sevko A, Sade-Feldman M, Kanterman J, Michels T, Falk CS, Umansky L, et al. Cyclophosphamide promotes chronic inflammation-dependent immunosuppression and prevents antitumor response in melanoma. J Invest Dermatol. 2013;133:1610–9.

    Article  CAS  PubMed  Google Scholar 

  22. Sevko A, Kremer V, Falk C, Umansky L, Shurin MR, Shurin GV, et al. Application of paclitaxel in low non-cytotoxic doses supports vaccination with melanoma antigens in normal mice. J Immunotoxico. 2012;9:275–81.

    Article  CAS  Google Scholar 

  23. Okada M. Subtyping lung adenocarcinoma according to the novel 2011 IASLC/ATS/ERS classification: correlation with patient prognosis. Thorac Surg Clin. 2013;23:179–86.

    Article  PubMed  Google Scholar 

  24. Detterbeck FC, Boffa DJ, Tanoue LT. The new lung cancer staging system. Chest. 2009;136:260–71.

    Article  PubMed  Google Scholar 

  25. Kusmartsev S, Nefedova Y, Yoder D, Gabrilovich DI. Antigen-specific inhibition of CD8+ T cell response by immature myeloid cells in cancer is mediated by reactive oxygen species. J Immunol. 2004;172:989–99.

    Article  CAS  PubMed  Google Scholar 

  26. Waight JD, Hu Q, Miller A, Liu S, Abrams SI. Tumor-derived G-CSF facilitates neoplastic growth through a granulocytic myeloid-derived suppressor cell-dependent mechanism. PLoS ONE. 2011;6:e27690.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Wang SY, Zhang Y, Yang YF, Du WL, Zhang H, Liu S, et al. The changes in myeloid-derived suppressor cells in mice with hepatic transplanted tumor and the regulatory effects of arsenious acid. Chin J Clin Oncol. 2010;37:194–7.

    Google Scholar 

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Acknowledgments

This work is supported by Natural Science Foundation of Liaoning Province (No. 201102296) provided by Ministry of Education.

Conflict of interest

None.

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Authors and Affiliations

  1. Department of Biotherapy and Laboratory of Biotherapy, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110032, China

    S. Wang, Y. Fu, C. Liu, X. Jiao, W. Du, H. Zhang & X. Wu

  2. Second Department of General Surgery, The Central Hospital of Yingkou, Yingkou, 115000, Liaoning, China

    K. Ma

Authors
  1. S. Wang
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  2. Y. Fu
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  3. K. Ma
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  4. C. Liu
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  5. X. Jiao
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  6. W. Du
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  7. H. Zhang
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  8. X. Wu
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Corresponding author

Correspondence to S. Wang.

Additional information

S. Wang and Y. Fu contributed equally to this work.

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Wang, S., Fu, Y., Ma, K. et al. The significant increase and dynamic changes of the myeloid-derived suppressor cells percentage with chemotherapy in advanced NSCLC patients. Clin Transl Oncol 16, 616–622 (2014). https://doi.org/10.1007/s12094-013-1125-y

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  • DOI: https://doi.org/10.1007/s12094-013-1125-y

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