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CD8+ TILs in NSCLC differentiate into TEMRA via a bifurcated trajectory, deciphering immunogenicity of tumor-antigens

ABSTRACT: CD8+ TILs in NSCLC differentiate into TEMRA via a bifurcated trajectory, deciphering immunogenicity of tumor-antigens

PROVIDER: PRJNA762913 | ENA |

REPOSITORIES: ENA

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CD8+ TILs in NSCLC differentiate into TEMRA via a bifurcated trajectory, deciphering immunogenicity of tumor-antigens

Project description:CD8+ tumor-infiltrating lymphocytes (TILs) comprise phenotypically and functionally heterogeneous subpopulations. Of these, effector memory CD45RA-expressing CD8+ T cells (Temra) have been discovered and characterized as the most terminally differentiated subset. However, their exact ontogeny and physiological importance in association with tumor progression remain poorly understood. We analyzed primary tumors and peripheral blood samples from 26 patients with non-small cell lung cancer and analyzed their phenotypes and functional characteristics using flow cytometry, RNA-sequencing, and bioinformatics. We found that tumor-infiltrating Temra (tilTemra) cells largely differ from peripheral blood Temra (pTemra), with distinct transcriptomes and functional properties. Notably, although majority of the pTemra was CD27-CD28- double-negative (DN), a large fraction of tilTemra population was CD27+CD28+ double-positive (DP), a characteristic of early-stage, less differentiated effector cells. Trajectory analysis revealed that CD8+ TILs undergo a divergent sequence of events for differentiation into either DP or DN tilTemra. Such a differentiation toward DP tilTemra relied on persistent expression of CD27 and CD28 and was associated with weak T cell receptor engagement. Thus, a higher proportion of DP Temra was correlated with lower immunogenicity of tumor antigens and consequently lower accumulation of CD8+ TILs. These data suggest a complex interplay between CD8+ T cells and tumors and define DP Temra as a unique subset of tumor-specific CD8+ TILs that are produced in patients with relatively low immunogenic cancer types, predicting immunogenicity of tumor antigens and CD8+ TIL counts, a reliable biomarker for successful cancer immunotherapy.

2021-09-14 | GSE184053 | GEO

Transcription profiling of human CD8 naive (TN), central memory (TCM), effector memory (TEM), and effector memory RA (TEMRA) T cells

Project description:Memory T cells are heterogeneous in terms of their phenotype and functional properties. We investigated the molecular profiles of human CD8 naïve (TN), central memory (TCM), effector memory (TEM), and effector memory RA (TEMRA) T cells using gene expression microarrays and phospho-protein-specific intracellular flow cytometry. We demonstrate that TCM have a gene expression and cytokine signaling signature that lies between that of TN and TEM or TEMRA cells, whereas TEM and TEMRA are closely related. Our data define the molecular basis for the different functional properties of central and effector memory subsets. We show that TEM and TEMRA cells strongly express genes with known importance in CD8 T cell effector function. In contrast, TCM are characterized by high basal and cytokine-induced STAT5 phosphorylation, reflecting their capacity for self-renewal. Altogether, our results distinguish TCM and TEM/TEMRA at the molecular level and are consistent with the concept that TCM represent memory stem cells.

2005-01-01 | E-TABM-40 | biostudies-arrayexpress

RNA-seq of KIR3DL3+ and KIR3DL3- CD8 terminally differentiated effect memory T cells (TEMRA)

Project description:The majority (60-97%) of KIR3DL3+ CD8 T cells belongs to TEMRA. To understand the function and characteristic of KIR3DL3+ CD8 T cells, we performed RNA-seq of KIR3DL3+ and KIR3DL3- CD8 TEMRA cells

2021-05-27 | GSE175550 | GEO

Clonally expanded CD8 T cells patrol Alzheimer's cerebrospinal fluid [TEMRA]

Project description:Alzheimer’s disease (AD) is an age-related neurodegenerative disorder in which neuroinflammation plays a critical function. Recurring viral infections and loss of immune competence increase risk for developing AD, yet the cellular and molecular mechanisms driving these immune changes are unknown. Here we performed mass cytometry of peripheral blood mononuclear cells and detected an immunologic signature of AD characterized by increased numbers of CD8+ T effector memory CD45RA+ (TEMRA) cells. CD8+ TEMRA cells were negatively associated with cognition and single cell RNA sequencing revealed their cytotoxic effector function. Strikingly, we discovered identical, shared T cell receptors (TCRs) of clonally expanded CD8+ TEMRA cells in cerebrospinal fluid (CSF) of three AD patients. Deep TCR sequencing, machine learning, and peptide screens identified the HLA-B*08:01-restricted Epstein-Barr virus trans-activator protein BZLF1 as the cognate antigen of a novel AD CSF TCR . These results provide the first evidence of clonal, antigen-specific T cells patrolling the intrathecal space of brains affected by age-related neurodegeneration

2019-11-04 | GSE134576 | GEO

Cytotoxic CD8+ Temra cells show loss of chromatin accessibility at genes associated with T cell activation

Project description:As humans age their memory T cell compartment expands due to lifelong exposure to antigens. This expansion is characterized by the presence of terminally differentiated CD8+ T cells (Temra) which possess an NK cell-like phenotype and are associated with chronic inflammatory conditions. Temra cells are predominantly driven by sporadic cytomegalovirus reactivation (CMV) yet their cellular heterogeneity remains understudied. To address this gap we measured their gene expression profiles and conducted single-cell transcriptome analysis. We show that CD8+ Temra cells are highly heterogeneous and describe subsets specific to old age and CMV infection.

2024-01-23 | GSE241493 | GEO

Transcriptomic profile of Traf6-deficient CD8+ TILs

Project description:Transcriptomic profile of sorted CD8+ TILs from Rag1-/- mice 4 days after transferred. Each group has two replicates.

2023-12-06 | GSE222539 | GEO

RNA-seq of T in PBMC and TILs

Project description:Purpose: Transcriptome profiling (RNA-seq) was used to compare the expression differences between T in PBMC and TILs Methods:Paired TILs and T in PBMC cells were sorted from fresh patient blood and tumor samples. Then the mRNA were sequeced using xTen platform. The sequence reads that passed quality filters were analyzed. Results: by extract mRNA from tumor infiltrated T cells from ovarian cancer patient sample and T cells from patient bllod samples, we compared the different expressed genes from TIL and T in blood. Hierarchical clustering of differentially expressed genes uncovered several as yet uncharacterized genes that may contribute to T cell exhausetion. Conclusions: We conclude that T in PBMC and TILs share different transcriptome characterization.

2022-12-18 | GSE157936 | GEO

Profiling of Naïve (CD45RA+CD28+), EM (CD45RA-CD28-) and TEMRA (CD45RA+CD28-) CD8+ T cells

Project description:RNAseq of 3 CD8 subsets (NAIVE, TEMRA and EM) from 8 paired Healthy Volunteers

2020-05-06 | GSE129356 | GEO

Transcriptomic profile of Traf6-deficient CD8+ TILs

Project description:Transcriptomic profile of Traf6-deficient CD8+ TILs

| PRJNA922497 | ENA

Characterization of gene expression of tumor infiltrating T cells (TILs) in previously untreated patients with follicular lymphoma (FL) compared with those of tonsils

Project description:It has been shown that tumor infiltrating immune cells have a profound impact on the outcome of FL. To find mechanisms whereby TILs are altered gene expession analysis of highly pure TILs were performed. The study is composed of 4 groups, FL CD4 (n=12), FL CD8 (n=9), Tonsil CD4 (n=7) and Tonsil CD8 (n=7). All FL patients were treatment naive. Cells were flowsorted from cryopreserved single cell suspensions and purity of cells were at least 95%.

2013-02-07 | E-GEOD-27928 | biostudies-arrayexpress

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