Immunotherapy of heterogenous sarcomas: questions and strategies

Development of immune therapy in sarcoma faces the rarity and heterogeneity of the disease. This review analyses the data available from published clinical trials, and the new clinical strategies under assessment, developed in parallel to the exploration of biological mechanisms underlying the efficacy of immune therapy.

Published data of four clinical trials assessing the efficacy of immune therapy in metastatic bone and soft-tissue sarcoma and associated translational programs are available. Response rate and progression-free survival with single-agent immune check point blockade in unselected sarcoma are low. No biomarkers of efficacy have been identified so far. To increase the efficacy of such treatments, combination of immune check point blockade with chemotherapy, radiotherapy or targeted therapy is currently assessed. Signal of specific sensibility of some histological subtypes is explored. Adoptive cell therapy or vaccine seems particularly promising in translocation-associated sarcoma.

Characterization of immune environment, mechanism of action of combined regimen and identification of biomarkers will be key steps to build the next clinical trials to improve the efficacy of such strategy.