Macrophage-Based Combination Therapies as a New Strategy for Cancer Immunotherapy.

Background: Cells of the immune system can inhibit tumor growth and progression; however, immune cells can also promote tumor cell growth, survival, and angiogenesis as a result of the immunosuppressive microenvironments. In the last decade, a growing number of new therapeutic strategies focused on reversing the immunosuppressive status of tumor microenvironments (TMEs), to reprogram the TME to be normal, and to further activate the antitumor functions of immune cells. Most of the "hot tumors" are encompassed with M2 macrophages promoting tumor growth, and the accumulation of M2 macrophages into tumor islets leads to poor prognosis in a wide variety of tumors.

Summary: Therefore, how to uncover more immunosuppressive signals and to reverse the M2 tumor-associated macrophages (TAMs) to M1-type macrophages is essential for reversing the immunosuppressive state. Except for reeducation of TAMs in the cancer immunotherapy, macrophages as central effectors and regulators of the innate immune system have the capacity of phagocytosis and immune modulation in macrophage-based cell therapies.

Key Messages: We review the current macrophage-based cell therapies that use genetic engineering to augment macrophage functionalities with antitumor activity for the application of novel genetically engineered immune cell therapeutics. A combination of TAM reeducation and macrophage-based cell strategy may bring us closer to achieving the original goals of curing cancer. In this review, we describe the characteristics, immune status, and tumor immunotherapy strategies of macrophages to provide clues and evidences for future macrophage-based immune cell therapies.