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

• Published in: Oncoimmunology Vol. 6; no. 6; p. e1309487
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 03.06.2017; Taylor & Francis Group
• Subjects: antitumor immunity; Drug-packaging microparticles; low-dose irradiation; macrophage remodeling; Original Research; tumor-repopulating cells; low-dose irradiation; Drug-packaging microparticles; macrophage remodeling; antitumor immunity; tumor-repopulating cells
• ISSN: 2162-4011; 2162-402X; 2162-402X
• DOI: 10.1080/2162402X.2017.1309487

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.