|
| Status |
Public on Oct 10, 2022 |
| Title |
Divergent outcomes of anti-PD-L1 treatment coupled with host-intrinsic differences in TCR repertoire and distinct T cell activation states in responding versus non-responding tumors |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
|
| Summary |
Differential responses to immune checkpoint inhibitors (ICI) may be attributed to tumor-intrinsic factors or environmental cues; however, these mechanisms cannot fully explain the variable ICI responses in different individuals. Here, we investigate the potential contribution of immunological heterogeneity with a focus on differences in T-cell receptor (TCR) repertoire to ICI responses, which has not been defined previously.
|
| |
|
| Overall design |
To reveal additional factors underlying heterogeneous responses to ICI, we employed a squamous cell carcinoma (SCC) mouse model in which tumor-bearing recipients unambiguously diverged into responders (R) or non-responders (NR) upon anti-PD-L1 treatment. We employed single-cell T-cell receptor (TCR) sequencing coupled with single-cell RNA sequencing to identify the difference in TCR repertoire of CD8 tumor infiltrating lymphocytes (TILs) in responders versus non-responders. Tumors and spleens were harvested from responders (n=4) and non-responders (n=4) and CD8 T cells were isolated and subjected for coupled scRNA-seq and single-cell TCR V(D)J sequencing (both CD8 TIL and splenic CD8 T cells) using 10× Genomics platform.
|
| |
|
| Contributor(s) |
John J, Wang JH |
| Citation(s) |
36330507 |
| |
| Submission date |
Sep 28, 2022 |
| Last update date |
Nov 17, 2022 |
| Contact name |
Jing Hong Wang |
| E-mail(s) |
jhw51@pitt.edu, wangj28@upmc.edu
|
| Phone |
412-864-7728
|
| Organization name |
University of Pittsburgh
|
| Department |
Department of Medicine
|
| Lab |
Jing Hong Wang Lab
|
| Street address |
5117 Centre Avenue, Suite 2.35
|
| City |
Pittsburgh |
| State/province |
PA |
| ZIP/Postal code |
15213-1862 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (32)
|
|
| Relations |
| BioProject |
PRJNA885044 |
Less...
More...