The Dichotomous Role of Bone Marrow Derived Cells in the Chemotherapy-Treated Tumor Microenvironment.

Bone marrow derived cells (BMDCs) play a wide variety of pro- and anti-tumorigenic roles in the tumor microenvironment (TME) and in the metastatic process. In response to chemotherapy, the anti-tumorigenic function of BMDCs can be enhanced due to chemotherapy-induced immunogenic cell death. However, in recent years, a growing body of evidence suggests that chemotherapy or other anti-cancer drugs can also facilitate a pro-tumorigenic function in BMDCs. This includes elevated angiogenesis, tumor cell proliferation and pro-tumorigenic immune modulation, ultimately contributing to therapy resistance. Such effects do not only contribute to the re-growth of primary tumors but can also support metastasis. Thus, the delicate balance of BMDC activities in the TME is violated following tumor perturbation, further requiring a better understanding of the complex crosstalk between tumor cells and BMDCs. In this review, we discuss the different types of BMDCs that reside in the TME and their activities in tumors following chemotherapy, with a major focus on their pro-tumorigenic role. We also cover aspects of rationally designed combination treatments that target or manipulate specific BMDC types to improve therapy outcomes.