Understanding the Origin and Diversity of Macrophages to Tailor Their Targeting in Solid Cancers

Abstract

Tumor-associated macrophages (TAMs) are a major component of the tumor immune microenvironment (TIME) and are associated with a poor prognostic factor in several cancers. TAMs promote tumor growth by facilitating immunosuppression, angiogenesis, and inflammation, and can promote tumor recurrence post-therapeutic intervention. Major TAM-targeted therapies include depletion, reprogramming, as well as disrupting the balance of macrophage recruitment and their effector functions. However, intervention-targeting macrophages have been challenging, since TAM populations are highly plastic and adaptation or resistance to these approaches often arise. Defining a roadmap of macrophage dynamics in the TIME related to tissue and tumor type could represent exploitable vulnerabilities related to their altered functions in cancer malignancy. Here, we review multiple macrophage-targeting strategies in brain, liver, and lung cancers, which all emerge in tissues rich in resident macrophages. We discuss the successes and failures of these therapeutic approaches as well as the potential of personalized macrophage-targeting treatments in combination therapies.

Keywords: immune phenotype; macrophage plasticity; macrophages; solid tumors; tumor immune microenvironment.