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Series GSE111414 Query DataSets for GSE111414
Status Public on Mar 01, 2021
Title KIR Polymorphism is Associated with Primary Resistance to PD-1 Blockade in Lung Cancer
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Adaptive immune escape of tumor cells by upregulation of ligands for programmed death 1 (PD-1) has been identified as an important and targetable pathway in many cancer types. Many clinical trials have demonstrated that targeting PD-1 or its ligand PD-L1 with immune checkpoint inhibitors (ICI) can restore anti-tumor immunity and induce durable remission. In patients with non-small cell lung cancer (NSCLC), several trials have demonstrated a survival benefit with ICI in patients with metastatic and locally advanced NSCLC.Yet, most patients have primary resistance to PD-1 or PD-L1 blockade during treatment: approximately 20% of unselected patients with NSCLC achieve a partial response while 40-50% have progressive disease as best response. Understanding mechanisms of primary resistance to PD-(L)1 blockade is important in the search for potentially targetable pathways and may ultimately allow discrimination between patients that benefit from PD-(L)1 blockade and those requiring combination or other approaches. We collected PBMCs and serum samples from 35 patients with NSCLC before and during PD-1 blockade treatment with nivolumab. We analyzed differentially expressed genes in CD8+ T cells from the peripheral blood of 5 patients with partial response and 5 patients with primary progressive disease to identify mechanisms of resistance to PD-1 therapy. Cells were collected from samples taken before and after 4 weeks of treatment.
Overall design Peripheral blood mononuclear cells (PBMCs) were prospectively collected from metastatic NSCLC patients (discovery cohort) just before the first administration (N1) and during treatment (at 4 weeks, N2) with PD-1 blockade. Patiens were classified to either "responder"(partial response PR) or "nonresponder" (progressive disease PD) based on objective radiological response by RECIST by a thoraic radiologist. From 5 responder and 5 nonresponder patients peripheral CD8+ T cells were sorted by fluorescence activated cell sorting using a BD FACS AriaIII and RNA isolated from these cells. We investigated changes in RNA expression upon treatment wit PD-1 blockade associated with clinical response.
Contributor(s) Läubli H, Trefny MP, Uhlenbrock F, Herzig P, Thommen DS, Savic S, Schaub S, Stenner F, Rothschild S, Zippelius A
Citation(s) 30765392
Submission date Mar 05, 2018
Last update date Apr 27, 2021
Contact name Heinz Läubli
Phone +41 61 556 5212
Organization name University of Basel
Department Department of Biomedicine
Lab Medical Oncology and Cancer Immunology
Street address Hebelstrasse 20
City Basel
ZIP/Postal code 4031
Country Switzerland
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (20)
GSM3030378 Patient BS373 timepoint N1
GSM3030379 Patient BS373 timepoint N2
GSM3030380 Patient BS375 timepoint N1
BioProject PRJNA436957
SRA SRP133939

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Supplementary file Size Download File type/resource
GSE111414_gene_counts.csv.gz 993.2 Kb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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