Synergistic effects of immune checkpoint therapy combinations in soft tissue sarcoma
Soft tissue sarcomas are a rare and heterogenic group of malignant neoplasms that account for about 1% of all cancers. The Myxofibrosarcoma is a subtype of soft tissue sarcomas and subject of my research. As soon as the tumor is considered to be irresectable or metastatic, the prognosis of patients drastically decreases due to a lack of effective chemotherapy which has barely been improved since the approval of Doxorubicin in 1974.
During the last years the tumor microenvironment has come into focus of research of many cancer entities. By modulating the infiltration and effectiveness of immune cells in the tumor microenvironment new therapeutic opportunities arose.
In many cases combinations of different immunotherapeutic approaches develop synergistic effects that lead to tumor reduction and improved patient survival.
In my project I want to explore synergistic effects of different immunomodulating therapy combinations to overcome acquired resistances. For this purpose, I established an orthotopic soft tissue sarcoma mouse model and investigated the effects on survival of Toll-like receptor agonists, adoptive cellular therapy and checkpoint-blockers like anti-PD-1 monoclonal antibodies.
A detailed analysis of the treated tumors will elucidate resistance mechanism and and underlying modifications within the tumor microenvironment.