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DACs
EGAC50000000202
DAC for study: "Combination pembrolizumab and radiotherapy induces systemic anti-tumor immune responses in immunologically-cold non-small cell lung cancer."
Contact Information
Valsamo Anagnostou
vanagno1@jhmi.edu
Request Access
This DAC controls 1 dataset
Dataset ID
Description
Technology
Samples
EGAD50000000404
The abscopal effects of radiation may sensitize immunologically “cold” tumors to immune checkpoint inhibition (ICI). We investigated the immunostimulatory effects of radiotherapy leveraging multi-omic analyses of serial tissue and blood biospecimens (n=293) from a phase 2 clinical trial of stereotactic body radiation therapy (SBRT) followed by pembrolizumab in metastatic non-small cell lung cancer (NSCLC; NCT02492568). Patients with immunologically-cold tumors (low tumor mutation burden, null PD-L1 expression, WNT-pathway mutated) in the SBRT arm had significantly longer progression-free survival compared to ICI alone (P<0.05). Induction of interferon-gamma, interferon-alpha, and antigen processing and presentation gene sets was significantly enriched post SBRT in non-irradiated tumor sites (FDR adjusted P<0.01). Significant on-therapy expansions of new and pre-existing TCR clones in both the tumor and blood compartments were noted in the SBRT arm (P<0.05). These findings support the systemic anti-tumor effects of immuno-radiotherapy and may open a therapeutic window of opportunity to overcome resistance to ICI.
Illumina HiSeq 2000
Illumina NovaSeq 6000
218