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Peripheral blood TCR clonotype diversity as an age-associated marker of breast cancer progression

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE239935 | GEO | 2023/11/09

REPOSITORIES: GEO

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Peripheral blood TCR clonotype diversity as an age-associated marker of breast cancer progression.

Project description:Immune escape is a prerequisite for tumor growth. We previously described a decline in intratumor activated cytotoxic T cells and T cell receptor (TCR) clonotype diversity in invasive breast carcinomas compared to ductal carcinoma in situ (DCIS), implying a central role of decreasing T cell responses in tumor progression. To determine potential associations between peripheral immunity and breast tumor progression, here, we assessed the peripheral blood TCR clonotype of 485 breast cancer patients diagnosed with either DCIS or de novo stage IV disease at younger (<45) or older (≥45) age. TCR clonotype diversity was significantly lower in older compared to younger breast cancer patients regardless of tumor stage at diagnosis. In the younger age group, TCR-α clonotype diversity was lower in patients diagnosed with de novo stage IV breast cancer compared to those diagnosed with DCIS. In the older age group, DCIS patients with higher TCR-α clonotype diversity were more likely to have a recurrence compared to those with lower diversity. Whole blood transcriptome profiles were distinct depending on the TCR-α Chao1 diversity score. There were more CD8+ T cells and a more active immune environment in DCIS tumors of young patients with higher peripheral blood TCR-α Chao1 diversity than in those with lower diversity. These results provide insights into the role that host immunity plays in breast cancer development across different age groups.

| S-EPMC10710020 | biostudies-literature

Peripheral blood TCR clonotype diversity as an age-associated marker of breast cancer progression (TCR)

Project description:Immune escape is a prerequisite of tumor growth. We previously described a decline in intratumor activated GZMB+CD8+ T cells and T cell receptor (TCR) clonotype diversity in invasive compared to in situ (DCIS) breast carcinomas implying a role for decreasing TCR diversity in tumor progression. Here, we evaluated peripheral blood TCR clonotype diversity in breast cancer patients diagnosed with DCIS or de novo stage IV disease at different ages. We found that peripheral TCR diversity is associated with clinicopathologic, and peripheral immune status and it correlates with the frequency of CD8+ T cells in DCIS of young patients. These results provide new insights to the role of host immunity and breast cancer development in different aged women.

2024-03-13 | GSE261515 | GEO

Peripheral blood TCR clonotype diversity as an age-associated marker of breast cancer progression (blood)

2023-11-09 | GSE239933 | GEO

Peripheral blood TCR clonotype diversity as an age-associated marker of breast cancer progression (tumor)

2023-11-09 | GSE239934 | GEO

Peripheral blood TCR clonotype diversity as an age-associated marker of breast cancer progression (TCR)

Project description:Peripheral blood TCR clonotype diversity as an age-associated marker of breast cancer progression (TCR)

| PRJNA1087365 | ENA

Peripheral blood TCR clonotype diversity as an age-associated marker of breast cancer progression (blood)

Project description:Peripheral blood TCR clonotype diversity as an age-associated marker of breast cancer progression (blood)

| PRJNA1001501 | ENA

Peripheral blood TCR clonotype diversity as an age-associated marker of breast cancer progression

Project description:Peripheral blood TCR clonotype diversity as an age-associated marker of breast cancer progression

| PRJNA1001408 | ENA

Peripheral blood TCR clonotype diversity as an age-associated marker of breast cancer progression (tumor)

Project description:Peripheral blood TCR clonotype diversity as an age-associated marker of breast cancer progression (tumor)

| PRJNA1001503 | ENA

Pan-cancer γδ TCR analysis uncovers clonotype diversity and prognostic potential.

Project description:Gamma-delta T cells (γδ T cells) play a crucial role in both innate and adaptive immunity within tumors, yet their presence and prognostic value in cancer remain underexplored. This study presents a large-scale analysis of γδ T cell receptor (γδ TCR) reads from 11,000 tumor samples spanning 33 cancer types, utilizing the TRUST4 algorithm. Our findings reveal extensive diversity in γδ TCR clonality and gene expression, underscoring the potential of γδ T cells as prognostic biomarkers in various cancers. We further demonstrate the utility of TCR gamma (TRG) and delta (TRD) gene expression from standard RNA-sequencing (RNA-seq) data. This comprehensive dataset offers a valuable resource for advancing γδ T cell research, with implications for enhanced immunotherapy approaches or alternative therapeutic strategies. Additionally, our centralized database supports translational research into the therapeutic significance of γδ T cells.

| S-EPMC11513832 | biostudies-literature

Dissection of the Human T-Cell Receptor γ Gene Repertoire in the Brain and Peripheral Blood Identifies Age- and Alzheimer's Disease-Associated Clonotype Profiles.

Project description:The immune system contributes to neurodegenerative pathologies. However, the roles of γδ T cells in Alzheimer's disease (AD) are poorly understood. Here, we evaluated somatic variability of T-cell receptor γ genes (TRGs) in patients with AD. We performed deep sequencing of the CDR3 region of TRGs in patients with AD and control patients without dementia. TRG clones were clearly detectable in peripheral blood (PB) and non-neuronal cell populations in human brains. TRG repertoire diversity was reduced during aging. Compared with the PB, the brain showed reduced TRGV9 clonotypes but was enriched in TRGV2/4/8 clonotypes. AD-associated TRG profiles were found in both the PB and brain. Moreover, some groups of clonotypes were more specific for the brain or blood in patients with AD compared to those in controls. Our pilot deep analysis of T-cell receptor diversities in AD revealed putative brain and AD-associated immunogenic markers.

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