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In the last few years, steps forward in the knowledge of the biology of soft tissue sarcomas (STS) have led to the development of new therapeutic strategies, including immunotherapy. This review outlines the recent findings on immunological features and provides a synopsis of the results of clinical trials with different immunotherapy approaches in STS, discussing criticisms, and how the efficacy of immunotherapy could be improved. The heterogeneity of STS has limited generalized approaches of immunotherapy in the disease. Clinical decisions should encompass a comprehensive characterization of the tumor microenvironment (TME), marked by intra-histotype diversity. Profiling of immune cells, checkpoint molecules, and antigen target/HLA expression is deemed to reshape the classical histotype classification for a selection of the most appropriate immune-based treatment. In a synergistic view, tumor-directed treatments, designed on the genetic and epigenetic histotype make-up, should be monitored for their immunomodulant effect and applied to ensure or amplify immunotherapy response. In light of the dynamic nature of the TME, this immunomonitoring should be conducted at baseline and during treatment, for improved therapeutic decisions and rational sequence of treatment combination, pursuing an immunological marker approach by histotype guidance.

Immunotherapy in soft tissue sarcoma: current evidence and future perspectives in a variegated family of different tumor