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

Transcriptome analysis of human peripheral blood T cells 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) andfunctional signatures in vivo in purified human T cells. Overall design: RNA extracted from freshly isolated T cells 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.