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| Status |
Public on Aug 07, 2024 |
| Title |
LAG3 and PD1 synergize on CD8+ T cells to drive T cell exhaustion and hinder autocrine IFN gamma-dependent anti-tumor immunity |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
Combined nivolumab (anti-PD1) and relatlimab (anti-LAG3) have shown enhanced effectiveness in melanoma patients. However, how these two receptors work together to hinder anti-tumor immunity remains unclear. Our study demonstrates that PD1/LAG3-deficient CD8+ T cells with more effectively clearing tumors and survive longer in melanoma mouse models. These PD1/LAG3-deficient CD8+ T cells have unique transcriptional profiles, broad TCR clonality, and enriched effector-like and interferon-responsive genes, leading to increased IFN gamma release indicating functionality. PD1 and LAG3 together drive T cell exhaustion, with a significant impact on TOX modulation. Mechanistically, autocrine IFN gamma signaling is crucial for enhancing anti-tumor immunity in PD1/LAG3-deficient CD8+ T cells, providing insights into the enhanced efficacy of combined PD1 and LAG3 targeting.
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| Overall design |
We employed single-cell RNA sequencing to profile CD8 cells from polyclonal/pMEL mice, both with and without single or double deficiencies of PD1 or LAG3. This comprehensive approach aimed to gain a deeper understanding of the enhanced efficacy observed in the melanoma model.
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| Web link |
https://www.cell.com/cell/abstract/S0092-8674(24)00776-1
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| |
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| Contributor(s) |
Andrews LP, Cui J, Vignali DA |
| Citation(s) |
39121848 |
| |
| Submission date |
Mar 28, 2024 |
| Last update date |
Aug 10, 2024 |
| Contact name |
Jian Cui |
| E-mail(s) |
cuij@pitt.edu
|
| Organization name |
University of Pittsburgh
|
| Department |
Immunology
|
| Lab |
Vignali Lab
|
| Street address |
5051 Centre Avenue
|
| City |
Pittsburgh |
| State/province |
PA |
| ZIP/Postal code |
15261 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
|
| Samples (5)
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| Relations |
| BioProject |
PRJNA1093086 |
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