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Tumor infiltrating CD8+ Tex cells dictate divergent survival outcomes in pre- vs post-menopausal ER+ breast cancer

ABSTRACT: Tumor infiltrating CD8+ Tex cells dictate divergent survival outcomes in pre- vs post-menopausal ER+ breast cancer

PROVIDER: PRJNA786200 | ENA |

REPOSITORIES: ENA

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Tumor infiltrating exhausted CD8+ T cells dictate divergent survival outcomes in pre- versus post-menopausal estrogen receptor-positive breast cancer

Project description: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.

2022-02-23 | GSE190202 | GEO

Tumor infiltrating CD8+ Tex cells dictate divergent survival outcomes in pre- vs post-menopausal ER+ breast cancer

Project description: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.

2022-02-23 | GSE190169 | GEO

Tumor infiltrating exhausted CD8+ T cells dictate divergent survival outcomes in pre- versus post-menopausal estrogen receptor-positive breast cancer

Project description:Tumor infiltrating exhausted CD8+ T cells dictate divergent survival outcomes in pre- versus post-menopausal estrogen receptor-positive breast cancer

| PRJNA786331 | ENA

Control vs. Menopausal kidney cortex

Project description:Gene expression in kidney cortex of control mice and menopausal mice 8 weeks after mice entered menopause. Menopause was induced by injection of 4-vinylcyclohexene diepoxide.

2010-09-14 | GSE20703 | GEO

Control vs. Menopausal kidney cortex

Project description:Gene expression in kidney cortex of control mice and menopausal mice 8 weeks after mice entered menopause. Menopause was induced by injection of 4-vinylcyclohexene diepoxide. Samples = 12

2010-09-14 | E-GEOD-20703 | biostudies-arrayexpress

Diabetic vs. Menopausal/diabetic kidney cortex

Project description:Gene expression in kidney cortex of diabetic mice and menopausal diabetic mice following 6 weeks of diabetes. Diabetes was induced with low-dose streptozotocin injections and menopause was induced by injection of 4-vinylcyclohexene diepoxide.

2010-09-14 | GSE20702 | GEO

Diabetic vs. Menopausal/diabetic kidney cortex

2010-09-14 | E-GEOD-20702 | biostudies-arrayexpress

CpG islands and GC content dictate nucleosome depletion in a transcription independent manner at mammalian promoters

Project description:This SuperSeries is composed of the following subset Series: GSE38560: CpG islands and GC content dictate nucleosome depletion in a transcription independent manner at mammalian promoters (RNA-seq) GSE38561: CpG islands and GC content dictate nucleosome depletion in a transcription independent manner at mammalian promoters (ChIP-seq) GSE38562: CpG islands and GC content dictate nucleosome depletion in a transcription independent manner at mammalian promoters (genomic SEQ) GSE38563: CpG islands and GC content dictate nucleosome depletion in a transcription independent manner at mammalian promoters (MNase-seq) GSE38564: CpG islands and GC content dictate nucleosome depletion in a transcription independent manner at mammalian promoters (5) Refer to individual Series

2012-06-11 | E-GEOD-38577 | biostudies-arrayexpress

Divergent clonal differentiation trajectories of T cell exhaustion (scRNA-seq)

Project description:T cells activated by chronic antigen exposure in the setting of viral infections or cancer can adopt an exhausted T cell (Tex) state, characterized by reduced effector function and proliferative capacity, and the upregulation of inhibitory receptors. However, whether all antigen-specific T cell clones follow the same molecular and cellular Tex differentiation trajectory remains unclear. Here, we generate a single-cell multi-omic atlas of T cell exhaustion that redefines the phenotypic diversity and molecular regulation of Tex phenotypes. Longitudinal analysis during chronic viral infection identifies an early effector phenotype that is epigenetically primed for Tex differentiation and two late-stage Tex cell states with either a terminal exhaustion or a killer cell lectin-like receptor (KLR)-expressing cytotoxic gene signature. We define clonal trajectories of antigen-specific T cells using paired single-cell RNA and T cell receptor sequencing and reveal distinct differentiation trajectories resulting in terminal Tex-biased, KLR Tex-biased, or divergent clones that differentiate into both phenotypes. Comparison of Tex phenotypes among shared T cell clones that traffic to multiple organs reveals that clonal differentiation trajectories are maintained across tissues. Finally, we show that differences in clonal differentiation trajectory are driven by TCR signaling avidity, whereby high-avidity T cell clones preferentially adopt a terminal Tex fate, while low-avidity clones adopt an effector-like KLR Tex fate. These findings reveal clonal heterogeneity in the T cell response to chronic antigen and genomic programs that underlie Tex fates and persistence.

2022-07-25 | GSE188666 | GEO

Microarray profile of osteoporosis related genes of Indian post menopausal females

Project description:Osteoporosis is a multifactorial disease with genetic and strong epigenetic component. In spite of enormous candidate gene association studies, the etiology and molecular mechanism of disease is not fully known. This study is undertaken to identify new markers of osteoporosis which could be vital in diagnosis and prognosis of disease, genome-wide microarray expression approach was employed on post menopausal Indian females living in same geographical area with almost similar life-style. To validate microarray gene expression pattern, qRT-PCR was performed on top 5 genes on osteoporotic (n =32) and non-osteoporotic (n=15) post menopausal females

2017-06-29 | GSE100609 | GEO

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