Exosomes in Immunotherapy Resistance
Abstract
The goal of the funded project is to test the role of tumor-derived exosomes (TDE) expressing immune checkpoint proteins in abrogating the ability of anti-PD1 or anti-PD-L1 antibodies from disrupting the tumor cell mediated suppression of T-cell cytotoxicity. To test our hypothesis, specific aim 1 focused on examining the expression of PD-L1 and other immune checkpoint proteins in lung tumor cell derived exosomes. Specific aim 2 focused investigating the immune modulation properties of tumor derived exosomes in vivo receiving anti-PD-L1 immunotherapy. Results from aim 1 studies showed TDE isolated from human non-small cell lung cancer (NSCLC) cell lines (H1299 and A549) were 100-150 nm in size, spherical with bilayer membrane, and had a negative charge. Transmission electron microscope showed TDE expressed PD-L1 on their surface. Immune checkpoint protein array optimization studies for determining the expression of immune-related proteins by TDE was performed. In vitro binding studies revealed anti-PD-L1 antibody bound to TDE as determined by changes in size and number of free exosomes. Finally, optimization of T-cell culture conditions for assessing TDE binding in the presence and absence of anti-PD-1/anti-PD-L1 antibody in vitro is completed.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2021
- Accession Number
- AD1170605
Entities
People
- Rajagopal Ramesh
Organizations
- University of Oklahoma Health Sciences Center