Reprograming Osteosarcoma Immune Landscape by STING and Lymphotoxin Receptor Agonists
Abstract
Immune checkpoint blockade has been mostly ineffective for osteosarcoma. The presence of tertiary lymphoid structure (TLS) in the tumor is thought to be essential for immunotherapy to be effective. TLS are found in tumors of some but not many osteosarcoma patients, raising a question how we can promote the development of such immunostimulatory tumor environment in the remaining population of osteosarcoma patients. We hypothesize that simultaneously activating STING and lymphotoxin beta receptor (LTbR) pathways promotes the formation of intratumoral high endothelial venules (HEVs) and TLS-like lymphoid structures in osteosarcoma, thereby reprograming the immune landscape of osteosarcoma to the one that is favorable for immune checkpoint inhibition therapies. Aim 1 will determine the osteosarcoma immune landscape created by STING/LTbR agonist combination therapy. Aim 2 will determine the effect of STING/LTbR agonist combination on osteosarcoma progression and examine whether this treatment sensitizes osteosarcoma to immune checkpoint inhibition
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1220614
Entities
People
- Masanobu Komatsu
Organizations
- Johns Hopkins University