Chemotherapeutic tumor microparticles combining low-dose irradiation reprogram tumor-promoting macrophages through a tumor-repopulating cell-curtailing pathway

Stem cell-like tumor-repopulating cells (TRCs) have a critical role in establishing a tumor immunosuppressive microenvironment. However, means to enhance antitumor immunity by disrupting TRCs are absent. Our previous studies have shown that tumor cell-derived microparticles (T-MPs) preferentially ab...

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Veröffentlicht in:Oncoimmunology 2017-06, Vol.6 (6), p.e1309487-e1309487
Hauptverfasser: Sun, Yanling, Zheng, Zu'an, Zhang, Huafeng, Yu, Yuandong, Ma, Jingwei, Tang, Ke, Xu, Pingwei, Ji, Tiantian, Liang, Xiaoyu, Chen, Degao, Jin, Xun, Zhang, Tianzhen, Long, Zhixiong, Liu, Yuying, Huang, Bo
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Sprache:eng
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Zusammenfassung:Stem cell-like tumor-repopulating cells (TRCs) have a critical role in establishing a tumor immunosuppressive microenvironment. However, means to enhance antitumor immunity by disrupting TRCs are absent. Our previous studies have shown that tumor cell-derived microparticles (T-MPs) preferentially abrogate TRCs by delivering antitumor drugs into nuclei of TRCs. Here, we show that low dose irradiation (LDI) enhances the effect of cisplatin-packaging T-MPs (Cis-MPs) on TRCs, leading to inhibiting tumor growth in different tumor models. This antitumor effect is not due to the direct killing of tumor cells but is T cell-dependent and relies on macrophages for their efficacy. The underlying mechanism is involved in therapeutic reprograming macrophages from tumor-promotion to tumor-inhibition by disrupting TRCs and curtailing their vicious education on macrophages. These findings provide a novel strategy to reset macrophage polarization and confer their function more like M1 than M2 types with highly promising potential clinical applications.
ISSN:2162-4011
2162-402X
2162-402X
DOI:10.1080/2162402X.2017.1309487