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Dendritic cells maintain anti-tumor immunity by positioning CD8 resident memory T cells in the skin through the CXCL16-CXCR6 axis

ABSTRACT: Tissue-resident memory (TRM) T cells are emerging as critical components of the immune response to cancer; yet, requirements for their ongoing function and maintenance remain unclear. Antigen presenting cells (APC) promote TRM cell differentiation and re-activation but have not been implicated in sustaining TRM cell responses. Here, we identified a novel role for dendritic cells in supporting tissue resident memory to melanoma. We showed that CD8 TRM cells remain in close proximity to dendritic cells in the skin. Depletion of CD11c+ cells results in rapid disaggregation and eventual loss of melanoma-specific TRM cells. Additionally, we determined that TRM migration and/or persistence requires chemotaxis and adhesion mediated by the CXCR6/CXCL16 axis. The interaction between CXCR6-expressing TRM cells and CXCL16-expressing APCs was found to be critical for sustaining TRM cell-mediated tumor protection. These findings substantially expand our knowledge of APC functions in tissue resident memory T cell homeostasis and longevity.

ORGANISM(S): Mus musculus

PROVIDER: GSE180647 | GEO | 2021/07/29

REPOSITORIES: GEO

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Dendritic cells maintain anti-tumor immunity by positioning CD8 resident memory T cells in the skin through the CXCL16-CXCR6 axis

Project description:Dendritic cells maintain anti-tumor immunity by positioning CD8 resident memory T cells in the skin through the CXCL16-CXCR6 axis

| PRJNA749023 | ENA

Single cell CITE-seq and VDJ sequencing of CD8+ central memory blood T cells (TCM) and their in-vivo matured tissue-resident memory-like T cells (TRM)

Project description:The aim of the experiment was to understand the clonal relationship between CD8+ central memory blood T cells (TCM) and the in-vivo matured TCM tissue-resident memory-like T cells (TRM) on day 14. TCM were FACS sorted from human PBMCs (n=5). Half of the cells were processed on day 1 and half of the cells of each donor were matured into TRM with anti-CD3, IL-15 and TGF beta for 14 days. Both day 1 TCM and matured day 14 TRM-like cells were further processed using the 5´10X genomics workflow.

2023-06-12 | E-MTAB-12840 | biostudies-arrayexpress

Molecular signature of brain resident memory CD8+ T cells

Project description:Tissue resident memory (Trm) represent a newly described memory T cell population. We have previously characterized a population of Trm that persists within the brain following acute virus infection. Although capable of providing marked protection against a subsequent local challenge, brain Trm do not undergo recall expansion following dissociation from the tissue. Furthermore, these Trm do not depend on the same survival factors as the circulating memory T cell pool as assessed either in vivo or in vitro. To gain greater insight into this population of cells we compared the gene-expression profiles of Trm isolated from the brain to circulating memory T cells isolated from the spleen following an acute virus infection. Trm displayed altered expression of genes involved in chemotaxis, expressed a distinct set of transcription factors and overexpressed several inhibitory receptors. Cumulatively, these data indicates that Trm are a distinct memory T cell population disconnected from the circulating memory T cell pool and displaying a unique molecular signature which likely results in optimal survival and function within their local environment. 13 samples were analyzed: 5 replicates of memory OT-I CD8+.CD103- T cells isolated from the spleen of mice on day 20 p.i. with VSV-OVA. 5 replicates of memory OT-I CD8+CD103+ T cells isolated from the brain of mice on day 20 p.i. with VSV-OVA; and 3 replicates of memory OT-I.CD8+ CD103- T cells isolated from the brain of mice on day 20 p.i. with VSV-OVA

2012-08-29 | E-GEOD-39152 | biostudies-arrayexpress

Development pathway for skin resident memory CD103+CD8+ T cells

Project description:Tissue resident memory T cells (TRM) provide superior protection against infection localised to extra-lymphoid compartments in the body. Here we show that CD103+CD8+ TRM cells develop in skin from killer cell lectin-like receptor (KLR)G1-negative precursors that selectively infiltrate the epithelial layer. In the skin, a combination of chemokine-guided epithelial entry, local interleukin (IL)-15 and transforming growth factor (TGF)-Î² signalling is required for formation and survival of these long-lived memory cells. Importantly, TRM differentiation results in the gradual acquisition of a unique transcriptional profile that differs from that expressed by memory cells in the circulation and other types of skin-resident intra-epithelial T cells, such as the dendritic epidermal T cells (DETC). We provide a comprehensive molecular and developmental framework for the local differentiation of a distinct type of peripheral memory T cell that contributes to an important first-line of immune defence in barrier tissues such as skin and mucosa. 24 samples were analyzed: 3 replicates of memory gB-T CD8+. CD103+ T cells isolated from the skin of C57/BL6 mice on day 30 p.i. with HSV KOS. 3 replicates of memory P14 CD8+ T cells isolated from gut of mice on day 60 p.i. with LCMV Armstrong. 3 replicates of memory gB-T CD8+ T cells from the lung of mice on day 30 p.i. with influenza WSN. 3 replicates of memory CD62L high CD8+ T cells from the spleen of mice on day 30 p.i. with HSV KOS. 3 replicates of memory CD62L low CD8+ T cells from the spleen of mice of day 30 p.i. with HSV KOS. 3 replicates of Î³Î´-DETC isolated from the skin of C57/BL6 mice on day 30 p.i. with HSV KOS. 3 replicates of Î±Î²-DETC from naive TCRÎ´-/- mice; and 3 replicates of naive gB-T CD8+ T cells from the spleen of naive gB-T transgenic mice.

2013-10-01 | E-GEOD-47045 | biostudies-arrayexpress

CXCR6 Positions Cytotoxic T Cells to Receive Critical Survival Signals in the Tumor Microenvironment

Project description:Cytotoxic T lymphocyte (CTL) responses against tumors are maintained by stem-like memory cells that self-renew, but also give rise to effector-like cells. The latter gradually lose their anti-tumor activity and acquire an epigenetically fixed, hypofunctional state, leading to tumor tolerance. Here, we show that the conversion of stem-like into effector-like CTL involves a major chemotactic reprogramming that includes the upregulation of chemokine receptor CXCR6. This receptor positions effector-like CTL in a discrete perivascular niche of the tumor stroma that is densely occupied by CCR7+ dendritic cells (DC) expressing the CXCR6 ligand CXCL16. CCR7+ DC also express and trans-present the survival cytokine IL-15. CXCR6 expression and IL-15 trans-presentation are critical for the survival and local expansion of effector-like CTL in the tumor microenvironment to maximize their anti-tumor activity before progressing to irreversible dysfunction. These observations reveal a cellular and molecular checkpoint that determines the magnitude and outcome of anti-tumor immune responses.

2021-06-30 | GSE179111 | GEO

Single cell 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). scRNAseq 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 scRNA-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.

2021-07-04 | GSE171161 | GEO

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.

2021-07-04 | GSE169237 | GEO

Single cell analysis reveals multiple subsets of CD8+ TRM and non-TRM cells with a type 17 signature in the inflamed psoriatic arthritis joint

Project description:CD69+CD103+ tissue-resident memory T-cells (TRM) are increasingly recognised as important drivers of inflammation. To decipher their potential role in inflammatory arthritis, we applied single cell, high-dimensional profiling (CyTOF and scRNAseq) to T-cells isolated from the joint of patients with psoriatic arthritis (PsA) or rheumatoid arthritis (RA). We identified three broad groups of synovial CD8+ TRM cells: cytotoxic and Treg-like TRM cells were present in the inflamed joints of patients with both PsA and RA, while CD161+CXCR6+ type 17-like TRM cells with a pro-inflammatory cytokine profile (IL-17A+TNFa+IFNg+) and a distinct transcriptomic signature and a polyclonal, but distinct TCR repertoire, were specifically enriched in the inflamed joints of patients with PsA. Type 17-like cells were also enriched in non-TRM CD8+ T-cells in PsA compared to RA. These findings add substantively to the accumulating evidence that the immunopathology of PsA and RA is different, with a particular role for type 17 cells in PsA.

2023-05-17 | GSE216914 | GEO

Development pathway for skin resident memory CD103+CD8+ T cells

2013-10-01 | GSE47045 | GEO

Single-cell sequencing of tissue-resident CD4+ T cells that drive compartmentalized immunopathology in the CNS

Project description:In chronic inflammatory diseases of the central nervous system (CNS), immune cells persisting behind the blood-brain barrier are supposed to promulgate local tissue destruction. The drivers of such compartmentalized inflammation remain unclear, but tissue-resident memory T cells (TRM) represent a potentially important cellular player in this process

2022-02-19 | E-MTAB-11422 | biostudies-arrayexpress

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