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

Abstract

<b><i>Background:</i></b> 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. <b><i>Summary:</i></b> 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. <b><i>Key Messages:</i></b> 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.

Targeting Myeloid Checkpoint Molecules in Combination With Antibody Therapy: A Novel Anti-Cancer Strategy With IgA Antibodies?

“…Such regulators are overexpressed on cancer cells to evade immune surveillance by myeloid immune cells. For example, the binding of CD47 to signal regulatory protein α (SIRPα) on macrophages reduces their anti-tumor response, which can be restored by blocking this interaction ( 10 ). Interestingly, SIRPα and other myeloid regulators are often also expressed on neutrophils, which are the most abundant immune cell in the circulation and are also found in many tumor cell infiltrates ( 11 ).…”

Interaction of RARRES1 with ICAM1 modulates macrophages to suppress the progression of kidney renal clear cell carcinoma

“…KIRC is a highly immunogenic tumor type whose tumor cells generate an immunosuppressive environment through multiple immunosuppressive mechanisms. KIRC tumors are surrounded by many inflammatory cells, such as T cells, NK cells, and For the application of novel immunotherapy, macrophagebased therapies could augment macrophage functionalities with antitumor activity (34). We found that both ICAM1 expression in RCC cells and Mac-1 expression in M1 macrophages were upregulated after RARRES1-overexpressing RCC cells were cocultured with macrophages.…”

Roles of exosomes as drug delivery systems in cancer immunotherapy: a mini-review

“…Macrophages are specialized, long-lived phagocytic cells of the innate immune system [ 153 , 154 ]. They are the largest immune cell population in solid tumors and play an important role in maintaining homeostasis [ 155 ]. Macrophages have two main polarization states: the proinflammatory M1 phenotype and the anti-inflammatory and reparative M2 phenotype [ 156 ].…”