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

ABSTRACT: Profiling of Naïve (CD45RA+CD28+), EM (CD45RA-CD28-) and TEMRA (CD45RA+CD28-) CD8+ T cells from kidney transplanted patients

PROVIDER: PRJNA814511 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18289325.fastq.gz	Fastqsanger.gz
	SRR18289325_1.fastq.gz	Fastqsanger.gz
	SRR18289325_2.fastq.gz	Fastqsanger.gz
	SRR18289326.fastq.gz	Fastqsanger.gz
	SRR18289326_1.fastq.gz	Fastqsanger.gz

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

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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.

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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.

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