The sarcoma immune landscape: Emerging challenges, prognostic significance and prospective impact for immunotherapy approaches

Abstract

Despite significant advances in multidisciplinary treatment strategies including surgery, radiotherapy, targeted therapy and chemotherapy there are yet no substantial improvements in the clinical benefit of patients with sarcomas. Current understanding of the underlying cellular and molecular pathways which govern the dynamic interactions between the tumor stroma, tumor cells and immune infiltrates in sarcoma tissues, led to the clinical development of new therapeutic options based on immunotherapies. Moreover, progress of the treatment of sarcomas also depends on the identification of biomarkers with prognostic and predictive values for selecting patients most likely to benefit from these new therapeutic treatments and also serving as potent therapeutic targets. Novel combinations with radiotherapy, chemotherapy, targeted therapy, vaccines, CAR-T cells and treatments targeting other immune components of the tumor microenvironment are underway aiming to bypass known resistance mechanisms. This review focuses on the role of tumor microenvironment in sarcoma, prognosis and response to novel immunotherapies.