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| Status |
Public on Sep 01, 2021 |
| Title |
Effects of durvalumab alone or combined with tremelimumab on preexisting cells in the tumor microenvironment |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Immune checkpoint blockade with anti–PD-1/L1 or anti–CTLA-4 therapies has shown promising results across multiple cancer types, but the mechanisms within the tumor microenvironment (TME) have not been fully characterized. We used single-cell RNA sequencing to investigate the effects of anti–PD-L1 monoclonal antibody (mAb) durvalumab (D) alone and combined with an anti–CTLA-4 mAb, tremelimumab (T), on distinct subsets of immune cells. Upon treatment with D or D+T, two NSCLC tumors showed elevated IFNγ responses, although they differed in magnitude of response but differed in other areas. Our results highlight that D and D+T in the TME have some consistent effects across tumors but also exhibit tumor-specific effects depending on composition and functional state of immune cells in the TME at time of treatment. This complex tumor-specific interplay of diverse immune subtypes in the TME is critical to better understand patient response to immunotherapy.
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| Overall design |
Two tumors were treated by Durva and Durva+Treme and underwent single cell sequencing. RNA sequencing of 97 advanced-stage non–small-cell lung carcinoma (NSCLC) biopsies from a nonrandomized phase 1b/2 clinical trial (1108/NCT01693562) were profiled to identify expression of genes of interest.
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| Contributor(s) |
Shrestha Y |
| Citation missing |
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| Submission date |
May 29, 2019 |
| Last update date |
Sep 01, 2021 |
| Contact name |
Yinong Sebastian |
| E-mail(s) |
sebastiany@medimmune.com
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| Organization name |
Medimmune
|
| Street address |
One MedImmune Way
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| City |
Gaithersburg |
| ZIP/Postal code |
20878 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA545340 |
| SRA |
SRP199793 |
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