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Contribution of resident and circulating precursors to tumor-infiltrating CD8+ T cell populations in lung cancer [scRNA-Seq]

ABSTRACT: Contribution of resident and circulating precursors to tumor-infiltrating CD8+ T cell populations in lung cancer [scRNA-Seq]

PROVIDER: PRJNA682052 | ENA |

REPOSITORIES: ENA

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Contribution of resident and circulating precursors to tumor-infiltrating CD8+ T cell populations in lung cancer

Project description:Contribution of resident and circulating precursors to tumor-infiltrating CD8+ T cell populations in lung cancer

| PRJNA682055 | ENA

Contribution of resident and circulating precursors to tumor-infiltrating CD8+ T cell populations in lung cancer [scTCR-seq]

Project description:Contribution of resident and circulating precursors to tumor-infiltrating CD8+ T cell populations in lung cancer [scTCR-seq]

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Contribution of resident and circulating precursors to tumor-infiltrating CD8+ T cell populations in lung cancer [scRNA-Seq]

Project description:Purpose: The goal of this study is to delineate the processes of CD8+ T cell differentiation in primary NSCLC by integrating transcriptomic and tcr profiles. Methods: A combination of single cell RNA and TCR sequencing (scRNA-seq and scTCR- seq) was used, in tumors, normal tissues adjacent to the tumor (juxta-tumor), and circulating blood derived from 11 patients with untreated, primary NSCLC. Results: We show that precursor, memory-like CD8+ TILs include 2 main populations: one is also present in the blood (circulating precursors); the other is also present in juxta-tumor tissue and bears markers of memory resident T cells (resident precursors). Both precursor subtypes differentiate into a main population of terminal effectors through a similar “transitional” stage. Terminal effectors are not observed in blood or juxta-tumor tissue, are more clonally expanded, and express signatures of exhaustion. A significant proportion of transitional and terminal effectors also express cell cycle signatures and Ki67, suggesting that clonal expansion occurs in situ is part of the terminal differentiation process.

2021-01-29 | GSE162498 | GEO

Contribution of resident and circulating precursors to tumor-infiltrating CD8+ T cell populations in lung cancer [scTCR-seq]

2021-01-29 | GSE162499 | GEO

Infiltrating monocyte-derived macrophages and resident kupffer cells display different ontogeny and functions in acute liver injury

Project description:Molecular profiling of infiltrating monocyte-derived macrophages versus resident kupffer cells following acute liver injury The liver has a remarkable capacity to regenerate after injury; yet, the role of macrophages (MF) in this process remains controversial mainly due to difficulties in distinguishing between different MF-subsets. Here, we utilized a murine model of acute liver injury caused by overdose of acetaminophen (APAP) and defined three distinct MF subsets that populate the liver following injury. Accordingly, resident Kupffer cells (KC) were significantly reduced upon APAP-challenge and started recovering by self-renewal at resolution phase without contribution of circulating Ly6Chi monocytes. The latter were recruited in a CCR2 and M-CSF mediated pathway at the necro-inflammatory phase and differentiated into ephemeral Ly6Clo MF subset at resolution phase. Moreover, their inducible ablation resulted in impaired recovery. Microarray based molecular profiling uncovered high similarity between steady state KC and those recovered at the resolution phase. In contrast, KC and monocyte-derived MF displayed distinct pro-restorative genetic signature at the resolution phase. Finally, we show that infiltrating monocytes acquire a pro-restorative polarization manifested by unique expression of pro-angiogenesis mediators and genes involved with inhibition of neutrophil activity and recruitment and promotion of their clearance. Collectively, our results present a novel phenotypic, ontogenic and molecular definition of liver-MF compartment following acute injury. 11 Samples (arrays) were performed. We generated pairwise comparison between all the different macrophages stages, using Partek Genomics Suite. Genes with p?5%[FDR] and a fold-change difference of ?2 or <-2 were selected.

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Contribution of resident and circulating precursors to tumor-infiltrating CD8+ T cell populations in lung cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-01-29 | GSE162500 | GEO

Infiltrating monocyte-derived macrophages and resident kupffer cells display different ontogeny and functions in acute liver injury

2014-08-01 | GSE55606 | GEO

Single cell RNA sequencing analysis of mouse resident and infiltrating immune cells during acute kidney injury and fibrosis

Project description:To obtain an unbiased characterization of the resident and infiltrating immune cell populations of mouse kidneys in healthy and diseased states, we performed single cell RNA-seq of facs-sorted CD45+ immune cells and CD4+ T cells from naïve and injured kidneys, at selected time points.

2020-01-31 | E-MTAB-8002 | biostudies-arrayexpress

Hobit identifies TRM precursors that are regulated by Eomes

Project description:Tissue-resident memory CD8+ T cells (TRM) constitute a non-circulating memory T cell subset that provides early protection against re-infection. However, how TRM arise from antigen-triggered T cells has remained unclear. Exploiting the TRM-restricted expression of Hobit, we developed TRM reporter/deleter mice to study TRM differentiation. We found that Hobit was upregulated in a subset of LCMV-specific T cells located within peripheral tissues during the effector phase of the immune response. These Hobit+ effector T cells were identified as TRM precursors, given that their depletion substantially decreased TRM development, but not the formation of circulating memory T cells. Adoptive transfer experiments of Hobit+ effector T cells corroborated their biased contribution to the TRM lineage. Transcriptional profiling of Hobit+ effector T cells underlined the early establishment of TRM properties including downregulation of tissue exit receptors and upregulation of TRM-associated molecules. Importantly, we identified Eomes as a key factor instructing the early bifurcation of circulating and resident lineages. These findings establish that commitment of TRM occurs early in antigen-driven T cell differentiation and reveal the molecular mechanisms underlying this differentiation pathway.

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Tissue-resident Memory and Circulating T cells are Early Responders to Pre-surgical Cancer Immunotherapy

Project description:Pre-surgical (neoadjuvant) immune checkpoint blockade has shown promising activity in multiple cancer types, but the molecular mechanisms are not well understood. Here, we characterized early kinetic changes in tumor-infiltrating and circulating immune cells in oral cancer patients treated with neoadjuvant anti-PD-1 or anti-PD-1/CTLA-4 in a phase 2 clinical trial. Tumor-infiltrating CD8 T cells that clonally expanded during immunotherapy expressed elevated tissue-resident memory and cytotoxicity programs compared to non-responding cells. These programs were already active in pre-treatment T cells that later responded, reflecting a capacity for rapid response. Treatment also induced a systemic immune response, including expansion of pre-existing and emergent T cell clonotypes undetectable prior to therapy. The frequency of activated blood CD8 T cells, including pretreatment PD-1-positive KLRG1-negative T cells, was strongly associated with intra-tumoral pathological response, and these activated cells were enriched for tumor-infiltrating T cell clonotypes. These results demonstrate how neoadjuvant checkpoint blockade induces local and systemic tumor immunity.

2022-07-07 | GSE200996 | GEO

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