Transcriptomics

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Gene Expression Profiling of human monocytes: Combination Therapy with Anti–CTLA-4 and Anti–PD-1 Leads to Distinct Immunologic Changes In Vivo


ABSTRACT: Transcriptome analysis of human peripheral blood monocytes Combination therapy concurrently targeting PD-1 and CTLA-4 immune checkpoints leads to remarkable antitumor effects. Although both PD-1 and CTLA-4 dampen the T cell activation, the in vivo effects of these drugs in humans remain to be clearly defined. To better understand biologic effects of therapy, we analyzed blood/tumor tissue from patients undergoing single or combination immune checkpoint blockade. We show that blockade of CTLA-4, PD-1, or combination of the two leads to distinct genomic (changes in gene-expression profile) and functional signatures in vivo in purified human T cells and monocytes. RNA extracted from freshly isolated monocytes from peripheral blood of patients treated with either anti–PD-1 (n = 6), anti–CTLA-4 (n = 5), Combo therapy with anti–PD-1 and anti–CTLA-4 concurrently (Combo, n = 6), and Seq anti–PD-1 in patients with prior anti–CTLA-4 (Seq, n = 3) was analyzed using the Affymetrix GeneChip Human Transcriptome 2.0 exon array. No techinical replicates were performed.

ORGANISM(S): Homo sapiens  

SUBMITTER: Rakesh Verma  

PROVIDER: E-GEOD-77924 | ArrayExpress | 2016-02-16

SECONDARY ACCESSION(S): GSE77924PRJNA312113

REPOSITORIES: GEO, ArrayExpress

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Publications

Combination therapy with anti-CTLA-4 and anti-PD-1 leads to distinct immunologic changes in vivo.

Das Rituparna R   Verma Rakesh R   Sznol Mario M   Boddupalli Chandra Sekhar CS   Gettinger Scott N SN   Kluger Harriet H   Callahan Margaret M   Wolchok Jedd D JD   Halaban Ruth R   Dhodapkar Madhav V MV   Dhodapkar Kavita M KM  

Journal of immunology (Baltimore, Md. : 1950) 20141224 3


Combination therapy concurrently targeting PD-1 and CTLA-4 immune checkpoints leads to remarkable antitumor effects. Although both PD-1 and CTLA-4 dampen the T cell activation, the in vivo effects of these drugs in humans remain to be clearly defined. To better understand biologic effects of therapy, we analyzed blood/tumor tissue from 45 patients undergoing single or combination immune checkpoint blockade. We show that blockade of CTLA-4, PD-1, or combination of the two leads to distinct genomi  ...[more]

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