Harnessing anti-tumor and tumor-tropism functions of macrophages via nanotechnology for tumor immunotherapy.

Reprogramming the immunosuppressive tumor microenvironment by modulating macrophages holds great promise in tumor immunotherapy. As a class of professional phagocytes and antigen-presenting cells in the innate immune system, macrophages can not only directly engulf and clear tumor cells, but also play roles in presenting tumor-specific antigen to initiate adaptive immunity. However, the tumor-associated macrophages (TAMs) usually display tumor-supportive M2 phenotype rather than anti-tumor M1 phenotype. They can support tumor cells to escape immunological surveillance, aggravate tumor progression, and impede tumor-specific T cell immunity. Although many TAMs-modulating agents have shown great success in therapy of multiple tumors, they face enormous challenges including poor tumor accumulation and off-target side effects. An alternative solution is the use of advanced nanostructures, which not only can deliver TAMs-modulating agents to augment therapeutic efficacy, but also can directly serve as modulators of TAMs. Another important strategy is the exploitation of macrophages and macrophage-derived components as tumor-targeting delivery vehicles. Herein, we summarize the recent advances in targeting and engineering macrophages for tumor immunotherapy, including (1) direct and indirect effects of macrophages on the augmentation of immunotherapy and (2) strategies for engineering macrophage-based drug carriers. The existing perspectives and challenges of macrophage-based tumor immunotherapies are also highlighted.