Department of Medicine, University of Minnesota Medical School, Box 286 University Hospital, Minneapolis, MN, 55455, USA.
Masonic Cancer Center, University of Minnesota Medical School, Minneapolis, MN, USA.
J Transl Med. 2019 Apr 18;17(1):130. doi: 10.1186/s12967-019-1883-6.
Cancer stem cells (CSC) may respond to chemotherapy differently from other tumor cells.
This study examined the expression of the putative cancer stem cell markers ALDH1, CD44, and CD133; the angiogenesis marker CD31; and the macrophage marker CD68 in soft tissue sarcomas (STS) before and after 4 cycles of chemotherapy with doxorubicin and ifosfamide in 31 patients with high-grade soft tissue sarcoma in a prospective clinical trial.
None of the markers clearly identified CSCs in STS samples. Macrophages represented a prominent component in viable tumor areas in pre-treatment STS biopsies, ranging from < 5 to > 50%. Furthermore, macrophages expressed CD44 and ALDH1. Macrophage density correlated with baseline maximum standardized uptake value (SUVmax) on fluoro-deoxyglucose positron emission tomography (PET) imaging. Pre-chemotherapy CD68 staining correlated positively with the baseline SUVmax, and negatively with the percent of viable tumor cells in post-chemotherapy resection samples. In particular, cases with more CD68-positive cells at biopsy had fewer viable tumor cells at resection, suggesting a better response to chemotherapy.
In conclusion, ALDH1, CD44, and CD133 are not likely to be useful markers of CSCs in STS. However, our observation of infiltrating macrophages in STS specimens indicates that these immune cells may contribute significantly to STS biology and response to chemotherapy, and could provide a potential target of therapy. Future studies should investigate macrophage contribution to STS pathophysiology by cytokine signaling.
癌症干细胞（CSC）可能对化疗的反应与其他肿瘤细胞不同。
本研究在一项前瞻性临床试验中，在 31 例高级软组织肉瘤患者中，检查了 4 个周期阿霉素和异环磷酰胺化疗前后，31 例高级软组织肉瘤患者的潜在癌症干细胞标志物 ALDH1、CD44 和 CD133；血管生成标志物 CD31；和巨噬细胞标志物 CD68 的表达。
在 STS 样本中，没有一种标志物能明确识别 CSC。在预处理 STS 活检中，巨噬细胞是存活肿瘤区域的主要成分，范围从 < 5%到 > 50%。此外，巨噬细胞表达 CD44 和 ALDH1。巨噬细胞密度与氟脱氧葡萄糖正电子发射断层扫描（PET）成像上的基线最大标准化摄取值（SUVmax）相关。化疗前 CD68 染色与基线 SUVmax 呈正相关，与化疗后切除样本中存活肿瘤细胞的百分比呈负相关。特别是，活检中 CD68 阳性细胞较多的病例，切除时存活肿瘤细胞较少，提示对化疗的反应较好。
总之，ALDH1、CD44 和 CD133 不太可能是 STS 中 CSC 的有用标志物。然而，我们在 STS 标本中观察到浸润性巨噬细胞表明，这些免疫细胞可能对 STS 的生物学和对化疗的反应有重要贡献，并可能为治疗提供潜在的靶点。未来的研究应该通过细胞因子信号研究巨噬细胞对 STS 病理生理学的贡献。
