Targeting tumor-associated macrophages for cancer immunotherapy.

Macrophages are important effector cells of the innate immune system and are also major components of the tumor microenvironment (TME). Macrophages that are abundant in the TME are called tumor-associated macrophages (TAMs). As TAMs promote strong tumor angiogenesis and support tumor cell survival, they are closely related to tumor growth. Several studies have demonstrated that reducing the density or effects of TAMs can inhibit the growth of tumors, making them targets for cancer immunotherapy, which has become a research hot spot. Several clinical and preclinical trials have studied drugs that inhibit the effects of and reduce the population of phagocytes that target TAMs achieve cancer immunotherapy. In this paper, we summarize the various methods of targeting TAMs for tumor immunotherapy, focusing on TAM mechanisms, sources, and polarization.

Shu Y ，Cheng P 《-》

Tumor-associated macrophages: A promising target for a cancer immunotherapeutic strategy.

Macrophages, a type of myeloid immune cell, play essential roles in fighting against pathogenic invasion and activating T cell-mediated adaptive immune responses. As a major constituent of the tumor microenvironment (TME), macrophages play a complex role in tumorigenesis and tumor progression. They can inhibit tumor growth by releasing proinflammatory cytokines and exerting cytotoxic activities but principally contribute to tumor progression by promoting tumor proliferation, angiogenesis, and metastasis. The tumor-promoting hallmarks of macrophages have aroused widespread interest in targeting tumor-associated macrophages (TAMs) for cancer immunotherapy. Increasing preclinical and clinical studies suggest that TAMs are a promising target for cancer immunotherapy. To date, TAM-targeted therapeutic strategies have mainly been divided into two kinds: inhibiting pro-tumor TAMs and activating anti-tumor TAMs. We reviewed the heterogeneous and plastic characteristics of macrophages in the TME and the feasible strategies to target TAMs in cancer immunotherapy and summarized the complementary effect of TAM-targeted therapy with traditional treatments or other immunotherapies.

Zhang SY ，Song XY ，Li Y ，Ye LL ，Zhou Q ，Yang WB ... -  《-》

Targeting tumor-associated macrophages as an antitumor strategy.

Tumor-associated macrophages (TAMs) are the most widely infiltrating immune cells in the tumor microenvironment (TME). Clinically, the number of TAMs is closely correlated with poor outcomes in multiple cancers. The biological actions of TAMs are complex and diverse, including mediating angiogenesis, promoting tumor invasion and metastasis, and building an immunosuppressive microenvironment. Given these pivotal roles of TAMs in tumor development, TAM-based strategies are attractive and used in certain tumor therapies, including inhibition of angiogenic signalling, blockade of the immune checkpoint, and macrophage enhancement phagocytosis. Several attempts to develop TAM-targeted agents have been made to deplete TAMs or reprogram the behaviour of TAMs. Some have shown a favourable curative effect in monotherapy, combination with chemotherapy or immunotherapy in clinical trials. Additionally, a new macrophage-based cell therapeutic technology was recently developed by equipping macrophages with CAR molecules. It is expected to break through barriers to solid tumor treatment. Although TAM-related studies have yielded positive antitumor outcomes, further investigations are needed to better characterize TAMs, which will benefit further establishment of novel strategies for tumor therapy. Here, we concisely summarize the functions of TAMs in the TME and comprehensively introduce the latest TAM-based regimens in cancer treatment.

Cheng N ，Bai X ，Shu Y ，Ahmad O ，Shen P ... -  《-》

The cross-talk between tumor-associated macrophages and tumor endothelium: Recent advances in macrophage-based cancer immunotherapy.

Tumor-associated macrophages (TAMs) are among the abundant cell populations of the tumor microenvironment (TME), which have pivotal roles in tumor development, chemoresistance, immune evasion, and metastasis. Growing evidence indicates that TAMs and the cross-talk between TAMs and tumoral endothelial cells can substantially contribute to tumor angiogenesis, which is considered a vital process for cancer development. Besides, tumoral endothelial cells can regulate the leukocyte infiltration to the TME in solid cancers and contribute to immune evasion. Therefore, targeting the immunosuppressive TAMs and the cross-talk between them can be a promising strategy for improving anti-tumoral immune responses. This review aims to summarize the biology of TAMs, their recently identified roles in tumor development/angiogenesis, and recent advances in macrophage-based cancer immunotherapy approaches for treating cancers.

Baradaran A ，Asadzadeh Z ，Hemmat N ，Baghbanzadeh A ，Shadbad MA ，Khosravi N ，Derakhshani A ，Alemohammad H ，Afrashteh Nour M ，Safarpour H ，Silvestris N ，Brunetti O ，Baradaran B ... -  《-》

Cancer Immunotherapy: Targeting Tumor-Associated Macrophages by Gene Silencing.

Zins K ，Abraham D 《-》