Targeting Tumor-Associated Macrophages in the Pediatric Sarcoma Tumor Microenvironment

Abstract

For many pediatric sarcoma patients, multi-modal therapy including chemotherapy, radiation, and surgery is sufficient to cure their disease. However, event-free and overall survival rates for patients with more advanced disease are grim, necessitating the development of novel therapeutic approaches. Within many pediatric sarcomas, the normal immune response, including recognition and destruction of cancer cells, is lost due to the highly immune suppressive tumor microenvironment (TME). In this setting, tumor cells evade immune detection and capitalize on the immune suppressed microenvironment, leading to unchecked proliferation and metastasis. Recent preclinical and clinical approaches are aimed at understanding this immune suppressive microenvironment and employing cancer immunotherapy in an attempt to overcome this, by renewing the ability of the immune system to recognize and destroy cancer cells. While there are several factors that drive the attenuation of immune responses in the sarcoma TME, one of the most remarkable are tumor associated macrophage (TAMs). TAMs suppress immune cytolytic function, promote tumor growth and metastases, and are generally associated with a poor prognosis in most pediatric sarcoma subtypes. In this review, we summarize the mechanisms underlying TAM-facilitated immune evasion and tumorigenesis and discuss the potential therapeutic application of TAM-focused drugs in the treatment of pediatric sarcomas.