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| Status |
Public on Oct 23, 2019 |
| Title |
Discovery of Specialized NK Cell Populations Infiltrating Human Melanoma Metastases |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
NK cells contribute to protective anti-tumor immunity, but little is known about the functional states of NK cells in human solid tumors. To address this issue, we performed single-cell RNA-seq analysis of NK cells isolated from human melanoma metastases, including lesions from patients who had progressed following checkpoint blockade. This analysis identified major differences in the transcriptional programs of tumor-infiltrating compared to circulating NK cells. Tumor-infiltrating NK cells represented seven clusters with distinct gene expression programs indicative of significant functional specialization, including cytotoxicity and chemokine synthesis programs. In particular, NK cells from three clusters expressed high levels of XCL1 and XCL2, which encode two chemokines known to recruit XCR1+ cross-presenting dendritic cells into tumors. In contrast, NK cells from two other clusters showed a higher level of expression of cytotoxicity genes. These data reveal key features of NK cells in human tumors and identify NK cell populations with specialized gene expression programs.
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| Overall design |
Matching samples were collected from blood and tumor-infiltrating NK cells in 5 patients with melanoma metastasis.
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| Contributor(s) |
Wucherpfennig KW |
| Citation(s) |
31801909 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 CA238039 |
Therapeutic Targeting of Immune Evasion from the MICA - NKG2D Pathway |
DANA-FARBER CANCER INSTITUTE |
Kai W Wucherpfennig |
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| |
| Submission date |
Oct 22, 2019 |
| Last update date |
Jan 22, 2020 |
| Contact name |
Yuheng Lu |
| E-mail(s) |
ylu@jimmy.harvard.edu
|
| Organization name |
Dana-Farber Cancer Institute
|
| Street address |
360 Longwood Ave
|
| City |
Boston |
| ZIP/Postal code |
02215 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
|
| Samples (12)
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| Relations |
| BioProject |
PRJNA578901 |
| SRA |
SRP226621 |
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