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| Status |
Public on Jun 28, 2017 |
| Title |
Immune escape in breast cancer during in situ to invasive carcinoma transition |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
To dissect mechanisms of immune escape during breast tumor progression, we analyzed the composition of leukocytes in normal breast tissues, ductal carcinomas in situ (DCIS), and HER2+ and triple negative invasive ductal carcinomas (IDC). We found significant tissue and tumor subtype-specific differences in multiple cell types including T cells and neutrophils. Analysis of gene expression profiles of T cells demonstrated enrichment for activated GZMB+MKI67+CD8+ effector T cell signatures in DCIS. TCR clonotypes also showed highest diversity in DCIS. Naïve T cell signatures predominated IDCs, especially triple negative subtypes. TIGIT and PDL1 immune checkpoint proteins showed differential expression between DCIS and IDCs with amplification of CD274 (encoding PDL1) only detected in triple negative IDCs. Our results imply that DCIS progression is limited by an anti-tumor immune response that becomes muted in invasive tumors due to selection for cancer cells and microenvironment that suppress activated T cells or no longer trigger their activation.
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| Overall design |
RNA-Seq: Gene expression analyses in leukocytes sorted from normal breast tissues, ductal carcinomas in situ (DCIS), and HER2+ and triple negative invasive ductal carcinomas (IDC).
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| Contributor(s) |
Gil Del Alcazar CJ, Huh SR, Ekram MB, Trinh A, Polyak K |
| Citation(s) |
28652380 |
| Submission date |
Sep 30, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Muhammad B Ekram |
| E-mail(s) |
muhammad_ekram@dfci.harvard.edu
|
| Organization name |
Dana-Farber Cancer Institute
|
| Department |
Medical Oncology
|
| Lab |
Kornelia Polyak Lab
|
| Street address |
450 Brookline Avenue, DA 740A
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
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| Platforms (2) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (41)
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| Relations |
| BioProject |
PRJNA345006 |
| SRA |
SRP090689 |
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