Uncovering the transcriptional changes in egressed vs intratumoral effector CD8+ T cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE203557 | GEO | 2023/01/20
REPOSITORIES: GEO
Similar Datasets
Project description:Uncovering the transcriptional changes in egressed vs intratumoral effector CD8+ T cells
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Project description:Flow sorted CD3+CD8+CD44+CXCR3+NKG2D+ lymph node cells from C3H/HeJ mice with alopecia were flow sorted and profiled in relation to CD3+CD8+CD44+CXCR3+NKG2D- lymph node cells from the same host Cell populations were sorted from three separate mice
2014-08-17 | E-GEOD-45657 | biostudies-arrayexpress
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2014-08-17 | GSE45657 | GEO
Project description:Effector CD8+ T cell (TE) proliferation and cytokine production depends on enhanced glucose metabolism. However, circulating T cells continuously adapt to glucose fluctuations caused by diet and inter-organ metabolite exchange. Here we show that transient glucose restriction (TGR) in activated CD8+ TE metabolically primes effector functions and enhances tumour clearance in mice. Tumor-specific TGR CD8+ TE co-cultured with tumor spheroids in replete conditions display enhanced effector molecule expression, and adoptive transfer of these cells in a murine lymphoma model leads to greater numbers of immunologically functional circulating donor cells and complete tumor clearance. Mechanistically, TGR TE undergo metabolic remodelling that upon glucose re-exposure supports enhanced glucose uptake, increased carbon allocation to the pentose phosphate pathway (PPP), and a cellular redox shift toward a more reduced state, all indicators of a more anabolic program to support their enhanced functionality. Thus, metabolic conditioning could be utilized to promote efficiency of T cell products for adoptive cellular therapy.
2020-08-03 | GSE152018 | GEO
Project description:Understanding the mechanisms underlying how T cells become dysfunctional in a tumor microenvironment (TME) will greatly benefit cancer immunotherapy. We found that increased CD36 expression in tumor-infiltrating CD8+ T cells, which was induced by TME cholesterol, was associated with tumor progression and poor survival in human and murine cancers. Genetic ablation of Cd36 in effector CD8+ T cells exhibited increased cytotoxic cytokine production and enhanced tumor eradication. CD36 mediated uptake of fatty acids by tumor-infiltrating CD8+ T cells in TME, induced lipid peroxidation and ferroptosis, and led to reduced cytotoxic cytokine production and impaired antitumor ability. Blocking CD36 or inhibiting ferroptosis in CD8+ T cells effectively restored their antitumor activity and, more importantly, possessed greater antitumor efficacy in combination with anti-PD-1 antibodies. This study reveals a new mechanism of CD36 regulating the function of CD8+ effector T cells and therapeutic potential of targeting CD36 or inhibiting ferroptosis to restore T cell function.
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Project description:For further validation that the circulating tumor cells (CTCs) from head and neck squamous cell carcinomas (HNSCC) patients were indeed cancer cells rather than non-specific contaminated cells such as white blood cells (WBCs), we examined the copy number alterations (CNAs) of the captured CTCs by aCGH (array comparative genomic hybridization).
2018-08-25 | GSE114122 | GEO
Project description:In this study, we performed single-cell transcriptomic profiling of mature PMN-MDSCs (mPMN-MDSCs) from non-small cell lung cancer (NSCLC) patients and identified a distinct cell cluster (NSCLC c6) exhibiting immunosuppressive and protumor features. Comparative analysis with publicly available single-cell RNA sequencing (scRNA-seq) datasets of tumor-associated neutrophils (TANs) revealed shared transcriptomic features between the identified NSCLC mPMN-MDSC and TAN clusters. These transcriptomic features included the expression of common genes, activation of the hypoxia signaling pathway, and metabolic reprogramming. Additionally, scRNA-seq analysis of mature immunosuppressive neutrophils from G-CSF-treated donors (GDs) – which are a reliable model of circulating mPMN-MDSCs - demonstrated similar dysregulation of hypoxia and metabolic pathways, further reinforcing the existence of transcriptomic similarities between circulating mPMN-MDSCs and TANs.
2025-07-09 | GSE293018 | GEO
Project description:We report the transcriptional profile of phosphatidylserine (PS) positive and PS negative CD44+CD62L- effector CD8+ T cells from LCMV-Armstrong infected mice sorted from spleens on day5 amd day10 after infection. PS was stained in vivo by injection of MFG-E8-eGFP. PS+ cells acquire PS through binding of extracellular vesicles (EVs). Binding of EVs by effector CD8+ T cells is strongly enhanced during LCMV infection and peaks between day5 and day10 post infection. Effector T cell gene signature is increased in EV+ CD8+ T cells compared to their EV- counterparts.
2023-03-29 | GSE201507 | GEO
Project description:Dendritic cells (DC) play a pivotal role in the induction and regulation of immune responses. In cancer, DC-based vaccines have proven to be safe and to elicit protective and therapeutic immunological responses. Recently, we showed that specific mTORC2 (mechanistic target of rapamycin complex 2) deficiency in DC enhances their ability to promote Th1 and Th17 responses after LPS stimulation. In the present study, bone marrow-derived mTORC2-deficient (Rictor(-/-)) DC were evaluated as a therapeutic modality in the murine B16 melanoma model. Consistent with their pro-inflammatory profile (enhanced IL-12p70 production and low PD-L1 expression versus control DC), intratumoral (i.t.) injection of LPS-activated Rictor(-/-) DC slowed B16 melanoma growth markedly in WT C57BL/6 recipient mice. This antitumor effect was abrogated when Rictor(-/-) DC were injected i.t. into B16-bearing Rag(-/-) mice, and also after selective CD8(+) T cell depletion in wild-type hosts in vivo, indicating that CD8(+) T cells were the principal regulators of tumor growth after Rictor(-/-) DC injection. I.t. administration of Rictor(-/-) DC also reduced the frequency of myeloid-derived suppressor cells within tumors, and enhanced numbers of IFNγ(+) and granzyme-B(+) cytotoxic CD8(+) T cells both in the spleens and tumors of treated animals. These data suggest that selective inhibition of mTORC2 activity in activated DC augments their pro-inflammatory and T cell stimulatory profile, in association with their enhanced capacity to promote protective CD8(+) T cell responses in vivo, leading to slowed B16 melanoma progression. These novel findings may contribute to the design of more effective DC-based vaccines for cancer immunotherapy.
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Project description:Cytotoxic T cells are typically expanded ex vivo for adoptive immunotherapy by culture with IL-2. This culture period leads to a differentiated phenotype and acquisition of effector function, as well as a loss of in vivo proliferative capability and anti-tumor efficacy. Here, we report antigen-specific and polyclonal expansion of cytotoxic T cells in a cocktail of cytokines and small molecules that leads to a memory-like phenotype in mouse and human cells even during extended culture, leading to enhanced in vivo expansion and tumor control. OT-I CD8 T cells were cultured for 14 days in either IL-2 or a cocktail of memory inducing small molecules and cytokines (IL-7, IL-21, 2-deoxyglucose and TWS119). Populations were sorted, IL-2 cells were CD44+CD62L-, cocktail cells were sorted into CD44+CD62L-, CD44+CD62L+ and CD44lowCD62L+ populations, and naive OT-I cells were CD44-CD62L+. Total RNA was extracted from each population and prepared for sequencing as three technical replicates.
2014-08-12 | E-GEOD-54877 | biostudies-arrayexpress