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Bulk RNA sequencing of TRM and ReCirculating CD8+ T cells from 7 HGSOC tumors

ABSTRACT: Purpose: Characterization of the gene expression profile of CD8+ TILs (TRM vs. re-circulating) from 7 HGSOC

ORGANISM(S): Homo sapiens

PROVIDER: GSE194383 | GEO | 2022/03/07

REPOSITORIES: GEO

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single-cell RNA and TCR sequencing of TRM CD8+ T cells sorted from 8 HGSOC tumors

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Bulk RNA sequencing of TRM and ReCirculating CD8+ T cells from 7 HGSOC tumors

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single-cell RNA and TCR sequencing of TRM CD8+ T cells sorted from 8 HGSOC tumors

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Bulk RNA sequencing of TCM, TEM, and TRM from CD8+CD44+GP33+ T cells after LCMV infection

Project description:During acute infections, CD8+ T cells form various memory subpopulations to provide long-lasting protection against reinfection. Central memory (TCM), Effector memory (TEM), and long-lived effector (LLE) cells are circulating memory populations with distinct plasticity, migration patterns, and effector functions. Tissue-resident memory (TRM) cells permanently reside in the frontline sites of pathogen entry and provide tissue-specific protection upon reinfection. Here, using scRNA-seq and bulk RNA-seq, we examined the different and shared transcriptomes and regulators of TRMs with other circulating memory populations. Furthermore, we identified heterogeneity within the TRM pool from small intestine and novel transcriptional regulators that may control the phenotypic and functional heterogeneity of TRM cells during acute infection. Our findings provide a resource for future studies to identify novel pathways for enhancing vaccination and immunotherapeutic approaches.

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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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Project description:single-cell RNA and TCR sequencing of TRM and ReCirulating CD8+ T cells sorted from 4 HGSOC tumors

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Bulk RNA-seq of tumor antigen specific CD8 Tissue Resident Memory (Trm) Cells

Project description:Purpose: To characterize the tumor-specific TRM cells in LNs, skin, lung and liver in mice with melanoma-associated vitiligo (MAV). Bulk RNA-seq was performed to identify populations of CD8 T cells with TRM transcriptional characteristics. Methods: CD8+THy1.1+ T cells were sorted from DLN, skin lung and liver of MAV mice and bulk RNA-sequenced Results: Heterogenouse CD8 memory populations with both circulatating and resident phenotypes were identified. Conclusions: Tumor-specific CD8 T cells form TRM responses in tumor-draining LNs.

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