Diaz-Montero C Marcela, Salem Mohamed Labib, Nishimura Michael I, Garrett-Mayer Elizabeth, Cole David J, Montero Alberto J
Department of Surgery, Medical University of South Carolina, Hollings Cancer Center, Charleston, SC, USA.
Cancer Immunol Immunother. 2009 Jan;58(1):49-59. doi: 10.1007/s00262-008-0523-4. Epub 2008 Apr 30.
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.
髓源性抑制细胞（MDSC）的异常蓄积是肿瘤免疫逃逸的重要机制。环磷酰胺（CTX）在无肿瘤动物中也已显示可导致MDSC短暂激增。对MDSC的了解主要基于临床前研究，迄今为止仅有少数已发表的研究涉及癌症患者。本研究的目的是检验以下假设：循环MDSC水平与临床癌症分期、基于CTX的化疗以及转移性肿瘤负荷相关。收集了106例新诊断的实体瘤患者（I-IV期）的全血。在开始全身治疗之前测定循环MDSC（Lin(-/Lo)，HLA DR-，CD33(+)CD11b(+)）的百分比。在17例每14天接受阿霉素-环磷酰胺化疗（ddAC）的早期乳腺癌患者中，在每个周期的第1天采集血液。与健康志愿者相比，所有分期的癌症患者循环MDSC均显著增加。还观察到循环MDSC与临床癌症分期之间存在显著相关性。此外，在IV期患者中，具有广泛转移性肿瘤负荷的患者MDSC百分比和绝对数量最高。与预处理水平相比，ddAC治疗后循环MDSC显著增加。循环MDSC水平与临床癌症分期、ddAC和转移性肿瘤负荷相关。该信息必须纳入未来探索基于免疫的治疗策略的试验设计中。未来的临床试验中也应测试对MDSC的药物调节作用。
