Facts and Hopes in Immunotherapy of Soft-Tissue Sarcomas

Sarcomas are mesenchymal tumors, encompassing more than 175 subtypes, each one with their own genetic complexities. As a result, immunotherapy approaches have not been universally successful across the wide range of diverse subtypes. The actual state of science and the current clinical data utilizing immunotherapy within the soft-tissue sarcomas (STS) will be detailed in this review. More precisely, the review will focus on: (i) the role of the immune microenvironment in the development and activity of new therapeutic approaches; (ii) the recent identification of the sarcoma immune class (SIC) groups, especially group SIC E with its B-cell signature that predicts immunotherapy response; (iii) the clinical trials using PD-1 and/or CTLA-4 inhibitors, which serves as reference for response data, (iv) the promising clinical activity from the combination of anti-angiogenics agents with PD-1 inhibitors, (v) the adapted T-cell therapies for synovial sarcoma that target either NY-ESO or MAGEA4; and (vi) the role for localized therapy using the virotherapy T-VEC with PD-1 inhibitors. Herein, we present the facts and the hopes for the patients with sarcoma, as the field is rapidly advancing its understanding of what and where to use the various types of immunotherapies.B.A. Van Tine was supported by the NCI (RO1CA227115)