Exploring the Tumor Microenvironment in Osteosarcoma: Driver of Resistance and Progression

Osteosarcoma (OS) is the most common bone-based cancer in both the US and the world in children, teenagers, and young adults. It is an aggressive form of sarcoma which forms mainly in the long bones of the legs and arms, often metastasizing prior to diagnosis. Every year across the globe, there are approximately 28,000 new cases, yet this sarcoma remains difficult to manage with standard treatments, partly due to its solid and immune resistant tumor microenvironment (TME). The quantity of research conducted on OS because of these difficulties has greatly increased over the past decade, meaning a comprehensive review of new findings on the TME may prove beneficial. This article aims to give a broad overview of the components of the TME of osteosarcoma, discuss its resistances and detrimental effects, and illustrate current and future immune therapy treatments which effectively target the microenvironment. Additionally, it will seek to highlight any knowledge gaps in the current literature and propose further studies to improve clinical outcomes. These studies could be beneficial in increasing drug and treatment efficacy for OS.