Unknown,Transcriptomics,Genomics,Proteomics

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Checkpoint blockade immunotherapy relies on T-bet but not Eomes to induce effector function in tumor infiltrating CD8+ T cells


ABSTRACT: Coinhibitory receptor blockade is a promising strategy to boost immunity against a variety of human cancers. However, many patients still do not benefit from this treatment, and responders often experience immune-related toxicities. These issues highlight the need for improved understanding of checkpoint blockade, but the T cell-intrinsic signaling pathways and gene expression profiles engaged during treatment are not well defined, particularly for combination approaches. We utilized a murine model of CD8+ T cell tolerance to address these issues. We used microarrays to examine the global transcriptional response of T cells rendered tolerant in vivo by encounter with tumor/self-antigen versus T cells activated in response to an immunogenic tumor. RNA isolated from naive Gag-specific T cells was compared to RNA isolated from T-cells transferred into B6 mice with established FBL tumor (immune) and from Alb:Gag mice (tolerant). Two days after T cell transfer, recipient spleen and lymph nodes were harvested and pooled. Transferred cells were then sorted based on CD8+ CD90.1+ CD69hi to a >96% purity using a FACSAria III (BD Biosciences). There were 3 biological replicates per condition.

ORGANISM(S): Mus musculus

SUBMITTER: Maureen Donlin 

PROVIDER: E-GEOD-58722 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Neuropilin-1 expression is induced on tolerant self-reactive CD8+ T cells but is dispensable for the tolerant phenotype.

Jackson Stephanie R SR   Berrien-Elliott Melissa M   Yuan Jinyun J   Hsueh Eddy C EC   Teague Ryan M RM  

PloS one 20141024 10


Establishing peripheral CD8(+) T cell tolerance is vital to avoid immune mediated destruction of healthy self-tissues. However, it also poses a major impediment to tumor immunity since tumors are derived from self-tissue and often induce T cell tolerance and dysfunction. Thus, understanding the mechanisms that regulate T cell tolerance versus immunity has important implications for human health. Signals received from the tissue environment largely dictate whether responding T cells become activa  ...[more]

Publication: 1/2

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