Dataset

Conserved interferon-gamma signaling and decreased immune exclusion programs in responses to immune checkpoint blockade therapy CM38-DNA

Dataset ID Technology Samples
EGAD00001006284 Illumina HiSeq 2000 70

Dataset Description

We analyzed baseline and on-therapy tumor biopsies from 101 patients with advanced melanoma treated with nivolumab (anti-PD-1) alone or combined with ipilimumab (anti-CTLA-4). Analysis of whole transcriptome data showed that T cell infiltration and interferon-gamma signaling signatures corresponded most highly with clinical response to therapy, with a reciprocal decrease in cell cycle and WNT signaling pathways in responding biopsies. Clinical outcome differences were likely not due to differential melanoma cell responses to interferon-gamma, as 57 human melanoma cell lines exposed in vitro to this cytokine showed a conserved interferon-gamma transcriptome response unless they had mutations that precluded signaling from the interferon-gamma receptor. Therefore, the magnitude of the antitumor T cell response and the corresponding downstream interferon-gamma signaling are the main drivers of clinical response or resistance to immune checkpoint blockade therapy.

Data Use Conditions

DS HMB

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Label Code Version Modifier
disease specific research DUO:0000007 2019-01-07 MONDO:0004992; MONDO:0005105
health or medical or biomedical research DUO:0000006 2019-01-07