Conserved interferon-gamma signaling and decreased immune exclusion programs in responses to immune checkpoint blockade therapy_CM38-DNA
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.
- 70 samples
- DAC: EGAC00001001667
- Technology: Illumina HiSeq 2000
- HMB DUO:0000006 (version: 2019-01-07)health or medical or biomedical researchThis data use permission indicates that use is allowed for health/medical/biomedical purposes; does not include the study of population origins or ancestry.
- DS DUO:0000007 (version: 2019-01-07)disease specific researchThis data use permission indicates that use is allowed provided it is related to the specified disease.ModifiersMONDO:0004992 MONDO:0005105
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Study ID | Study Title | Study Type |
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EGAS00001004548 | Other |
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