Effect of chemotherapy on cancer stem cells and tumor-associated macrophages in a prospective study of preoperative chemotherapy in soft tissue sarcoma

Keith M Skubitz, Jon D. Wilson, Edward Y Cheng, Bruce R. Lindgren, Kristin L Boylan, Amy P Skubitz

Research output: Contribution to journalReview articlepeer-review

5 Scopus citations


Background: Cancer stem cells (CSC) may respond to chemotherapy differently from other tumor cells. Methods: 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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Article number130
JournalJournal of Translational Medicine
Issue number1
StatePublished - Apr 18 2019

Bibliographical note

Funding Information:
Supported in part by the Karen Wyckoff Rein in Sarcoma Foundation, the Kevin Franklin family, and the James Dinnerstein family. The funding sources had no role in the design, data collection, analysis, or interpretation of the data or manuscript writing.

Publisher Copyright:
© 2019 The Author(s).

Copyright 2019 Elsevier B.V., All rights reserved.


  • Cancer stem cell
  • Chemotherapy
  • Macrophage
  • PET
  • Positron emission tomography
  • Sarcoma

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