Abstract A07: Combining CTLA4 and PD-L1 blockade leads to complete eradication of metastatic osteosarcoma

Osteosarcoma remains one of the most common bone cancers in children and adolescents. While conventional therapy can be effective at reducing or stabilizing primary osteosarcoma tumors, metastatic disease is typically refractory to treatment. Previously, we have investigated the role of PD-1 in limiting the efficacy of CTL to mediate metastatic osteosarcoma immune control. Blockade of PD-1/PD-L1 interactions in metastatic osteosarcoma dramatically improves survival outcomes by enhancing the function of osteosarcoma-specific CTL. However, PD-1/PD-L1 blockade treated mice still succumb to disease due to the development of PD-L1 antibody resistance. Combinational CTLA-4 and PD-L1 blockade treated mice were able to completely eradicate metastatic osteosarcoma, and generate immunity to disease. These results suggest that blockade of PD-1/PD-L1 interactions in patients with metastatic osteosarcoma may lead to tumor resistance, requiring combinational immunotherapies to combat disease. Citation Format: Danielle M. Lussier, John L. Johnson, Pooja Hingorani, Joseph N. Blattman. Combining CTLA4 and PD-L1 blockade leads to complete eradication of metastatic osteosarcoma. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr A07.