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| Status |
Public on Jan 10, 2019 |
| Title |
Tumor-resident memory-like CD8 T cells represent an essential cellular target for cancer immunotherapy |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Persistent exposure to high levels of antigen results in the progressive exhaustion of T cells and has been thought to preclude the formation of memory. In contrast to the latter assumption, we show here that tumor-specific CD8 T cells residing in the tumor microenvironment include a Tcf1 expressing sub population that has key characteristics of central memory cells, lack an effector cell signature but display hallmarks of exhausted T cells, including the expression co-inhibitory receptors such as PD1. Similar memory-like cells are identified in melanoma patients. Preclinical mouse models reveal that the expansion of tumor-specific CD8 T cells, the production of terminally differentiated exhausted CD8 T cells and sustained tumor control in response to therapeutic vaccination or immune checkpoint blockade critically depends on the presence of these memory-like CD8 T cells. Tumor immune responses thus harbor tumor resident memory-like CD8 T cell populations, which can be therapeutically targeted to improve immune control of cancer.
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| Overall design |
Naive Tcf7-GFP+ P14 cells (CD45.2) (Naive) were transferred into B6 recipient mice (CD45.1) one day prior to sub-cutaneous implantation of B16-gp33 tumor cells. When tumors became palpable mice were vaccinated with pg33 peptide plus poly(I:C). Six days later Tcf7-GFP+ P14 cells and Tcf7-GFP- P14 cells amongst tumor infiltrating lymphocytes (TIL) were flow sorted. Total RNA was extracted, cDNA libraries prepared and sequencing was performed using Illumina HiSeq 2500 technology.
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| Contributor(s) |
Siddiqui I, Calderon-Copete S, Pradervand S, Held W |
| Citation(s) |
30635237 |
| |
| Submission date |
May 18, 2018 |
| Last update date |
Jul 30, 2019 |
| Contact name |
Sandra Calderon |
| Organization name |
University of Lausanne
|
| Department |
Center for Integrative Genomics
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| Lab |
Lausanne Genomics Technologies Facility
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| Street address |
Génopode Building
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| City |
Lausanne |
| ZIP/Postal code |
1015 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (11)
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| Relations |
| BioProject |
PRJNA472005 |
| SRA |
SRP148417 |
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