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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE239934 | GEO | 2023/11/09

REPOSITORIES: GEO

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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)

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Immune escape in breast cancer during in situ to invasive carcinoma transition

Project description: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.

2017-06-28 | GSE87517 | GEO

Single cell transcriptomic and T cell repertoire analysis reveals trajectory of tumor - infiltrating lymphocyte states in pancreatic cancer

Project description: The CD8+ TIL contained a putative transitional GZMK+ population based on TCR clonotype sharing, and cell-state trajectory analysis showed similarity to a GZMB+PRF1+ cytotoxic and a CXCL13+ dysfunctional population. Statistical analysis suggested that certain TIL states, such as dysfunctional and inhibitory populations, often occurred together. Finally, analysis of cultured TIL revealed that high-frequency clones from effector populations were preferentially expanded. These data provide a framework for understanding the PDAC TIL landscape for future TIL use in immunotherapy for PDAC.

2022-09-06 | GSE211644 | GEO

Single-cell analysis of human MAIT cell transcriptional, functional and clonal diversity [Exp 1]

Project description:MAIT cells are innate-like T cells that recognize microbial metabolites through a semi-invariant T cell receptor (TCR). Major questions remain regarding the extent of human MAIT cell functional and clonal diversity. To address these, we analyzed the single-cell transcriptome and TCR repertoire of blood and liver MAIT cells and developed functional RNA-sequencing (fRNA-seq), a method to integrate function and TCR clonotype at single-cell resolution. MAIT cell clonal diversity was comparable to conventional memory T cells, with private TCR repertoires shared across matched tissues. Baseline functional diversity was low and largely related to tissue site. MAIT cells showed stimulus-specific transcriptional responses in vitro, with cells positioned along gradients of activation. Clonal identity influenced resting and activated transcriptional profiles, but intriguingly was not associated with the capacity to produce IL-17. Overall, MAIT cells show phenotypic and functional diversity according to tissue localization, stimulation environment, and clonotype.

2023-08-14 | GSE194187 | GEO

Single-cell analysis of human MAIT cell transcriptional, functional and clonal diversity [ATAC-seq]

Project description:Mucosal-associated invariant T (MAIT) cells are innate-like T cells that recognize microbial metabolites through a semi-invariant T cell receptor (TCR). Major questions remain regarding the extent of human MAIT cell functional and clonal diversity. To address these, we analyzed the single-cell transcriptome and TCR repertoire of blood and liver MAIT cells and developed functional RNA sequencing, a method to integrate function and TCR clonotype at single-cell resolution. MAIT cell clonal diversity was comparable to conventional memory T cells, with private TCR repertoires shared across matched tissues. Baseline functional diversity was low and largely related to tissue site. MAIT cells showed stimulus-specific transcriptional responses in vitro, with cells positioned along gradients of activation. Clonal identity influenced resting and activated transcriptional profiles but intriguingly was not associated with the capacity to produce IL- 17. Overall, MAIT cells show phenotypic and functional diversity according to tissue localization, stimulation environment and clonotype.

2023-08-14 | GSE238139 | GEO

Single-cell analysis of human MAIT cell transcriptional, functional and clonal diversity [Exp 3]

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Single-cell analysis of human MAIT cell transcriptional, functional and clonal diversity [Exp 4]

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Single-cell analysis of human MAIT cell transcriptional, functional and clonal diversity [Exp 2]

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Gene expression of TCR-alpha/beta CD4- CD8- human T cells

Project description:The origin and function of human double negative (DN) TCR-alpha/beta T cells is unknown. They are thought to contribute to the pathogenesis of systemic lupus erythematosus because they expand and accumulate in inflamed organs. Here we provide evidence that human TCR-alpha/beta CD4- CD8- DN T cells derive exclusively from activated CD8+ T cells. Freshly isolated TCR-alpha/beta DN T cells display a distinct gene expression and cytokine production profile. DN cells isolated from peripheral blood as well as DN cells derived in vitro from CD8+ T cells, produce a defined array of pro-inflammatory mediators that includes IL-1, IL-17, IFN-gama, CXCL3, and CXCL2. These results indicate that, upon activation, CD8+ T cells have the capacity to acquire a distinct phenotype that grants them inflammatory capacity. TCR-alpha-beta+ CD25- T cells from healthy human individuals were sorted into CD4+, CD8+, and CD4-CD8- T cells. Cell lysis and RNA extraction was performed immediately. RNA from each cell subset was pooled.

2009-05-16 | E-GEOD-16130 | biostudies-arrayexpress

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