Uncovering the transcriptional changes in egressed vs intratumoral effector CD8+ T cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE203557 | GEO | 2023/01/20
REPOSITORIES: GEO
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Project description:Uncovering the transcriptional changes in egressed vs intratumoral effector CD8+ T cells
| PRJNA841374 | ENA
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: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:Effector cells for adoptive immunotherapy can be generated by in vitro stimulation of naïve or memory subsets of CD8+ T cells. While the characteristics of CD8+ T cell subsets are well defined, the heritable influence of those populations on their effector cell progeny is not well understood. We studied effector cells generated from naïve or central memory CD8+ T cells and found that they retained distinct gene expression signatures and developmental programs. Effector cells derived from central memory cells tended to retain their CD62L+ phenotype, but also to acquire KLRG1, an indicator of cellular senescence. In contrast, the effector cell progeny of naïve cells displayed reduced terminal differentiation, and, following infusion, they displayed greater expansion, cytokine production, and tumor destruction. These data indicate that effector cells retain a gene expression imprint conferred by their naïve or central memory progenitors, and they suggest a strategy for enhancing cancer immunotherapy. Experiment Overall Design: Effector cells were generated from naive or central memory CD8+ T cells. The cells were then rested (unstimulated) or restimulated (stimulated). This experimental design resulted in 4 groups (Naïve-derived/stimulated, Naïve-derived/unstimulated, Central memory-derived/stimulated, Central memory-derived/unstimulated). Three replicates from independent experiments were analyzed.
2009-06-23 | E-GEOD-16522 | biostudies-arrayexpress
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
Project description:Effector cells for adoptive immunotherapy can be generated by in vitro stimulation of naïve or memory subsets of CD8+ T cells. While the characteristics of CD8+ T cell subsets are well defined, the heritable influence of those populations on their effector cell progeny is not well understood. We studied effector cells generated from naïve or central memory CD8+ T cells and found that they retained distinct gene expression signatures and developmental programs. Effector cells derived from central memory cells tended to retain their CD62L+ phenotype, but also to acquire KLRG1, an indicator of cellular senescence. In contrast, the effector cell progeny of naïve cells displayed reduced terminal differentiation, and, following infusion, they displayed greater expansion, cytokine production, and tumor destruction. These data indicate that effector cells retain a gene expression imprint conferred by their naïve or central memory progenitors, and they suggest a strategy for enhancing cancer immunotherapy.
2009-06-10 | GSE16522 | GEO
Project description:Naïve CD44-lo/CD62L-hi/CD8+ T cells from C3H.SW mice were compared to CD44-hi/CD82L-lo/CD8+ effector memory T cells and CD44-lo/CD62L-hi/CD8+ postmitotic T cells, using 3 biological replicates of each type of sample. The later two cells types were highly purified at day 14 after transplantation from GVHD B6/SJL mice receiving donor C3H.SW mouse-derived naive CD44-lo/CD62L-hi/CD8+ T cells and T cell-depleted bone marrow. Recipient mice had first been lethally irradiated at a dose of 10Gy in two fractions. This is a MHC-identical minor histocompatibility antigen-mismatched mouse GVHD model of human allogeneic hematopoietic stem cell transplantation. Naive T cell samples were from pools of 2 mice each, while effector memory and postmitotic T cell samples were purified from pools of T cells from 4 mice each. After RNA extraction and cleanup, biotin labeled cRNA was prepared from 600 ng total RNA, using two rounds of in vitro transcription, and hybridized to Affymetrix Mouse Genome 430A 2.0 arrays using standard techniques. Keywords: Cell type comparison 9 samples were analyzed on 9 Affymetrix microarrays to assay mRNA levels. There were 3 biological replicates of each of 3 different cell types.
2010-06-08 | E-GEOD-13743 | biostudies-arrayexpress
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
2014-08-17 | GSE45657 | GEO
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
Project description:During a T cell response, naïve CD8 T cells differentiate into effector cells. Subsequently, a subset of effector cells termed memory precursor effector cells (MPECs) further differentiates into functionally mature memory CD8 T cells. The transcriptional network underlying this carefully scripted process is not well understood. Here, we report that the transcription factor FoxO1 plays an integral role in facilitating effector to memory transition and functional maturation of memory CD4 and CD8 T cells. We find that FoxO1 is not required for differentiation of effector cells, but in the absence of FoxO1, memory CD8 T cells displayed features of scenescence and progressive attrition in polyfunctionality, which in turn led to impared recall responses and poor protective immunity. These data suggest that FoxO1 is essential for active maintenance of functional CD8 T cell memory and protective immunity. Under competing conditions in bone marrow Single-cell suspensions from splenocytes of eight samples WT (control) and FoxO1-/- (experimental) LCMV-immune mice were prepared using standard procedures. CD8 T cells were then isoloated using Thy1.2 (CD90.2) (30-H12) microbeads (Miltenyi Biotec). Cells were then stained with anti-CD8, anti-CD44 and Db/NP396 MHC class I tetramer. Activated (CD8+CD44hi), naive (CD8+CD44lo), and virus-specific CD8 T cells were sorted using FACSAria II instrument (BD Biosciences). The purity of the cells was >95%. Total RNA was extracted from the sorted cells by Trizol Reagent. RNA samples were reverse transcribed and Cy3-labeled cDNAs were hyrbidized to Agilent whole Mouse Genome Oligo Microarrays. Fluorscence signals were detected using Agilent's Microarray Scanner system, data was analyzed using the Rosetta Resolver gene expression data analysis system and genes with a fold change < and p-values <0.01 were identified. Microarray data discussed in the paper is focused on virus-specific memory CD8 T cells from samples WT_Tet_2 vs KO_Tet_2.
2013-06-25 | E-GEOD-45673 | biostudies-arrayexpress