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| Status |
Public on Feb 23, 2022 |
| Title |
Tumor infiltrating exhausted CD8+ T cells dictate divergent survival outcomes in pre- versus post-menopausal estrogen receptor-positive breast cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
CD8+ tumor infiltrating lymphocytes (TILs) are associated with improved survival in triple negative breast cancer (TNBC), yet have no association with survival in estrogen receptor-positive (ER+) BC. The basis for these contrasting findings remains elusive. We identify subsets of BC tumors infiltrated by CD8+ T cells with characteristic features of exhausted T cells (TEX). Tumors with abundant CD8+ TEX exhibit a distinct tumor microenvironment marked by amplified interferon-γ signaling related pathways and higher PD-L1 expression. Paradoxically, high levels of CD8+ TEX TILs associate with decreased overall survival ER+ BC patients, but not TNBC patients. Moreover, high tumor expression of a CD8+ TEX signature identifies dramatically reduced survival in pre-menopausal, but not post-menopausal, ER+ BC patients. Finally, we demonstrate the value of a tumor TEX signature score in identifying high-risk pre-menopausal ER+ BC patients amongst those with intermediate Oncotype Dx breast recurrence scores. Our data highlight the complex relationship between CD8+ TILs, interferon-γ signaling, and estrogen receptor status in BC patient survival. This work identifies pre-menopausal ER+ BC patients with high levels of tumor infiltrating CD8+ TEX as a high-risk subset that may benefit from immunotherapy strategies.
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| Overall design |
We employed single cell sequencing of patient CD8+ T cells from 10 different BC patients, including 9 primary tumors, 2 T+LNs, 3 NCBTs, and 7 matched PBMCs samples. CD8+ T cells stained for PD-1, CD39, CD103, CD69, CD137, and CCR7 were single cell index sorted for downstream whole transcriptome analysis. Unbiased Seurat cluster analysis found CD8+ T cells to be composed of four major clusters with discrete gene expression patterns.
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| Contributor(s) |
Guo W, Egelston CA, Lee PP |
| Citation(s) |
35132960 |
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| Submission date |
Dec 05, 2021 |
| Last update date |
Mar 21, 2022 |
| Contact name |
Peter P Lee |
| E-mail(s) |
plee@coh.org
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| Phone |
6262182519
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| Organization name |
Beckman Research Institute at City of Hope
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| Department |
Immuno-Oncology
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| Street address |
1500 E. Duarte Rd.
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| City |
Duarte |
| State/province |
CA |
| ZIP/Postal code |
91010 |
| Country |
USA |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (19)
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| Relations |
| BioProject |
PRJNA786331 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE190202_imputed_count.csv.gz |
5.0 Mb |
(ftp)(http) |
CSV |
| GSE190202_meta_data.txt.gz |
10.9 Kb |
(ftp)(http) |
TXT |
| GSE190202_raw_count.txt.gz |
2.5 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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