Immunotherapy in tumors failing check-point inhibitors:the sarcoma example – What we missed and where we are heading

Abstract

The introduction of immune checkpoint inhibitors represented a true revolution in the treatment of melanoma and a few other cancer subtypes. Unfortunately, the use of these drugs did not achieve the same beneficial results in other neoplasms, such as soft tissue sarcoma and gastrointestinal stromal tumor. These failures encouraged deeper research into the complex interactions between cancer and host immune system, to try to shed light on the ability of cancer cells to escape immunologic surveillance. Key elements to explain tumor immune escape were found in the tumor microenvironment. The main actors in this complex network are lymphocytes, cytokines and innate immunity cells such as macrophages and antigen presenting cells. Thus, immuno-oncologists are studying the different components of the tumor microenvironment to identify possible new therapeutic targets. In this paper, we summarize the most important aspects of these interactions, and provide an overview of the newer and more promising immunotherapeutic strategies.