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ABSTRACT
Despite identification of macrophages in tumors (tumor-associated macrophages, TAM) as potential targets for cancer therapy, the origin and function of TAM in the context of malignancy remain poorly characterized. Here, we show that microparticles (MPs), as a by-product, released by tumor cells act as a general mechanism to mediate M2 polarization of TAM. Taking up tumor MPs by macrophages is a very efficient process, which in turn results in the polarization of macrophages into M2 type, not only leading to promoting tumor growth and metastasis but also facilitating cancer stem cell development. Moreover, we demonstrate that the underlying mechanism involves the activation of the cGAS/STING/TBK1/STAT6 pathway by tumor MPs. Finally, in addition to murine tumor MPs, we show that human counterparts also possess consistent effect on human M2 polarization. These findings provide new insights into a critical role of tumor MPs in remodeling of tumor microenvironment and better understanding of the communications between tumors and macrophages.
Disclosure of potential conflicts of interest
No potential conflicts of interest were disclosed.
Author contributions
RM, TJ, DC, WD, HZ, XY, JM, XL, YZ and YL designed and performed the experiments and analyzed the data. TJ, GS and XQ analyzed the data. RM and BH designed the experiments, interpreted the results and wrote the manuscript.
Funding
This work was supported by National Basic Research Program of China (2014CB542100), National Science Fund for Distinguished Young Scholars of China (81225021), National Natural Science Foundation of China (81502415, 81472653), Special Fund of Health Public Welfare Profession of China (201302018), and Soundny (Sheng-Qi-An) Biotech (Wuhan, China).