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GEO help: Mouse over screen elements for information. |
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| Status |
Public on May 17, 2024 |
| Title |
Circadian tumor infiltration and function of CD8+ T cells dictate a temporal response to immunotherapy |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The quantity and quality of tumor-infiltrating lymphocytes (TILs), particularly CD8+ T cells, are parameters linked to tumor control and response to immunotherapy. Yet, it is unknown whether these parameters are controlled in a circadian manner. Here, we show in murine and human cancers that the phenotype and number of TILs show time-of-day differences, which are driven by rhythmic leukocyte infiltration and depend on the circadian clock machinery. These rhythms can be harnessed therapeutically: chimeric antigen receptor (CAR) T cells or immune checkpoint blockers produce significant antitumor benefits when administered at the optimal time of the day, but have little effect when administered at other times. Furthermore, time-of-day-dependent T cell signatures in murine tumor models predict overall survival in melanoma patients and correlate with response to anti-PD-1 therapy. Our data provide unexpected evidence of circadian dynamics in the tumor microenvironment (TME), and suggest the importance of exploiting them in prospective clinical trials.
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| Overall design |
Tumors were harvested at different times of the day and tumor infiltrating leukocytes were isolated by fluorescence activated cell sorting: live CD45+ cells. Tumor infiltrating leukocytes were sequenced by scRNA-seq and analyzed.
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| Web link |
https://www.cell.com/cell/fulltext/S0092-8674(24)00410-0
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| Contributor(s) |
Wang C, Zeng Q, Gul ZM, Wang S, Pick R, Cheng P, Bill R, Wu Y, Naulaerts S, Barnoud C, Hsueh P, Moller SH, Cenerenti M, Sun M, Su Z, Jemelin S, Petrenko V, Dibner C, Hugues S, Jandus C, Li Z, Michielin O, Ho P, Garg AD, Simonetta F, Pittet MJ, Scheiermann C |
| Citation(s) |
38723627 |
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| Submission date |
Feb 29, 2024 |
| Last update date |
May 17, 2024 |
| Contact name |
Christoph Scheiermann |
| Organization name |
UNIGE
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| Street address |
1, rue Michel Servet
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| City |
Genève |
| ZIP/Postal code |
1211 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (8)
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| GSM8121408 |
TIL, ZT7, replicate 2 |
| GSM8121409 |
TIL, ZT13, replicate 1 |
| GSM8121410 |
TIL, ZT13, replicate 2 |
| GSM8121411 |
TIL, ZT19, replicate 1 |
| GSM8121412 |
TIL, ZT19, replicate 2 |
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| Relations |
| BioProject |
PRJNA1082390 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE260641_seu_obj_all_merged_filtered_processed_pop_def_man_1_alt_obj.rds.gz |
1.2 Gb |
(ftp)(http) |
RDS |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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