Journal
CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 58, Issue 1, Pages 49-59Publisher
SPRINGER
DOI: 10.1007/s00262-008-0523-4
Keywords
Immature myeloid cells; Myeloid-derived suppressor cells; Breast cancer; Cancer; Cyclophosphamide; Tumor burden; Cytokines; PBMC; T cells
Categories
Funding
- Hollings Cancer Center [R01CA83672]
- NATIONAL CANCER INSTITUTE [R01CA083672] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Abnormal accumulation of myeloid-derived suppressor cells (MDSC) is an important mechanism of tumor immune evasion. Cyclophosphamide (CTX) has also been shown in non-tumor bearing animals to cause transient surges in MDSC. Knowledge of MDSC is primarily based on preclinical work, and to date only few published studies have involved cancer patients. The goal of this study was to test the hypothesis that circulating MDSC levels correlate with clinical cancer stage, CTX-based chemotherapy, and metastatic tumor burden. Whole blood was collected from 106 newly diagnosed solid tumor patients (stages I-IV). Percentages of circulating MDSC (Lin(-/Lo), HLA DR, CD33(+)CD11b(+)) were determined prior to initiation of systemic therapy. In 17 early stage breast cancer patients receiving doxorubicin-cyclophosphamide chemotherapy every 14 days (ddAC) blood was collected on day 1 of each cycle. Circulating MDSC were significantly increased in cancer patients of all stages relative to healthy volunteers. A significant correlation between circulating MDSC and clinical cancer stage was also observed. Moreover, among stage IV patients, those with extensive metastatic tumor burden had the highest percent and absolute number of MDSC. Significant increases in circulating MDSC were observed with ddAC when compared with pretreatment levels. Circulating MDSC levels correlate with clinical cancer stage, ddAC, and metastatic tumor burden. This information must be incorporated into the design of future trials exploring immune-based therapeutic strategies. Pharmacologic modulation of MDSC should also be tested in future clinical trials.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available