The blood mMDSC to DC ratio is a sensitive and easy to assess independent predictive factor for epithelial ovarian cancer survival
| Autor: | V E van der Noord, J J van Ham, S.H. van der Burg, Saskia J. A. M. Santegoets, Marij J. P. Welters, Judith R. Kroep, A.F. de Groot, A M Carnaz Simões, Eveline M. Dijkgraaf |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
lcsh:Immunologic diseases. Allergy
0301 basic medicine epithelial ovarian cancer mMDSC to DC ratio Myeloid medicine.medical_treatment Immunology CD33 lcsh:RC254-282 survival 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Immunology and Allergy Medicine Leukocytosis predictive Original Research Chemotherapy business.industry Immunotherapy lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Gemcitabine Carboplatin 030104 developmental biology medicine.anatomical_structure Oncology chemistry leukocytosis 030220 oncology & carcinogenesis Cancer research Myeloid-derived Suppressor Cell medicine.symptom lcsh:RC581-607 business medicine.drug |
| Zdroj: | OncoImmunology Oncoimmunology OncoImmunology, 7(8) OncoImmunology, Vol 7, Iss 8 (2018) |
| Popis: | Epithelial ovarian cancer (EOC) may cause abnormal blood levels of leukocytes. This paraneoplastic manifestation is associated with a worse response to therapy and shorter survival. To understand the complexity and nature of these leukocytes, we dissected the different populations of myeloid cells and analyzed their relation to clinical outcome. Therefore, baseline blood samples of 36 EOC patients treated either with carboplatin/doxorubucin or with gemcitabine were analyzed for different subsets of monocytes/macrophages, myeloid derived suppressor cells (MDSC) and dendritic cells (DC) using multiparameter flow cytometry as well as functional assays for myeloid cell mediated suppression of antigen-specific T cell reactivity. Healthy donor blood served as control. EOC patients displayed an increase in monocytes/macrophages, monocytic MDSC (mMDSC) and CD33-CD11b+CD14-CD15- double-negative MDSC (CD33- dnMDSC) and a decrease in the frequency of DC, across all EOC subtypes. A low frequency of DC and high frequencies of monocytes/macrophages and mMDSC, but not CD33- dnMDSC, were associated with poor overall survival. Patient's monocytes/macrophages and mMDSC, but not CD33- dnMDSC, were shown to suppress T cell reactivity in vitro. The mMDSC and DC frequencies were not altered upon treatment. Importantly, the mMDSC to DC ratio was the strongest independent, highly sensitive and specific, predictive factor for survival. This was irrespective of the type of chemotherapy or disease stage and outperformed classical parameters as WHO status or time from last chemotherapy. Thus, the baseline blood mMDSC to DC ratio is a robust, independent and easy to analyze predictive factor for EOC survival, and may assist patient selection for immunotherapy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|