Cancer Immunotherapy: Targeting Tumor-Associated Macrophages by Gene Silencing

Abstract

Tumor-associated macrophages (TAMs) are representing a major leukocyte population in solid tumors. Macrophages are very heterogeneous and plastic cells and can acquire distinct functional phenotypes ranging from antitumorigenic to immunosuppressive tumor-promoting M2-like TAMs, depending on the local tissue microenvironment (TME). TAMs express cytokines, chemokines, growth factors, and extracellular matrix (ECM) modifying factors, and the cross talk with the TME regulates pathways involved in the recruitment, polarization, and metabolism of TAMs during tumor progression. Due to their crucial role in tumor growth and metastasis, selective targeting of TAM for the treatment of cancer with therapeutic agents that promote phagocytosis or suppress survival, proliferation, trafficking, or polarization of TAMs may prove to be beneficial in cancer therapy. In this chapter, we will discuss TAM biology and current strategies for the targeting of TAMs using small interfering RNA (siRNA)-based drugs. In the past few years, advances in the field of nanomedicine pave the way for the development of siRNA-based drugs as an additional class of personalized cancer immuno-nanomedicines. Fundamental challenges associated with this group of therapeutics include the development process, delivery system, and clinical translation for siRNA-based drugs.