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| Status |
Public on Aug 10, 2017 |
| Title |
Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade [WES] |
| Organism |
Mus musculus |
| Experiment type |
Genome variation profiling by high throughput sequencing
|
| Summary |
Immune checkpoint blockade is able to achieve durable responses in a subset of patients, however we lack a satisfying comprehension of the underlying mechanisms of anti-CTLA-4 and anti-PD-1 induced tumor rejection. To address these issues we utilized mass cytometry to comprehensively profile the effects of checkpoint blockade on tumor immune infiltrates in human melanoma and murine tumor models. These analyses reveal a spectrum of tumor infiltrating T cell populations that are highly similar between tumor models and indicate that checkpoint blockade targets only specific subsets of tumor infiltrating T cell populations. Anti-PD-1 predominantly induces the expansion of specific tumor infiltrating exhausted-like CD8 T cell subsets. In contrast, anti-CTLA-4 induces the expansion of an ICOS+ Th1-like CD4 effector population in addition to engaging specific subsets of exhausted-like CD8 T cells. Thus, our findings indicate that anti-CTLA-4 and anti-PD-1 checkpoint blockade induced immune responses are driven by distinct cellular mechanisms.
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| Overall design |
Mouse cell lines B16BL6 and MC38 were analyzed using whole exome sequencing
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| Contributor(s) |
Wei S, Wei SC, Levine JH, Cogdill AP, Zhao Y, Anang NA, Andrews MC, Sharma P, Wang J, Wargo JA, Pe’er D, Allison JP, Ramagli L |
| Citation(s) |
28803728 |
| Submission date |
Jul 05, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Spencer Wei |
| E-mail(s) |
SCWei@mdanderson.org
|
| Phone |
7135633295
|
| Organization name |
MD Anderson Cancer Center
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| Department |
Immunology
|
| Street address |
7455 Fannin St.
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| City |
Houston |
| State/province |
TX |
| ZIP/Postal code |
77054 |
| Country |
USA |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (2) |
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| This SubSeries is part of SuperSeries: |
| GSE100809 |
Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade |
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| Relations |
| BioProject |
PRJNA393131 |
| SRA |
SRP111109 |
