A Th1/IFNγ Gene Signature Is Prognostic in the Adjuvant Setting of Resectable High-Risk Melanoma but Not in Non–Small Cell Lung Cancer

A Th1/IFNγ Gene Signature Is Prognostic in the Adjuvant Setting of Resectable High-Risk Melanoma but Not in Non–Small Cell Lung Cancer.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1158/1078-0432.CCR-18-3717
Journal or Publication Title: Clinical Cancer Research
Volume: 26
Number: 7
Page Range: pp. 1725-1735
Date: 2019
Divisions: Melanoma Oncology and Immunology
Depositing User: General Admin
Identification Number: 10.1158/1078-0432.CCR-18-3717
ISSN: 1078-0432
Date Deposited: 04 Jan 2021 01:21
Abstract:

Purpose: Immune components of the tumor microenvironment (TME) have been associated with disease outcome. We prospectively evaluated the association of an immune-related gene signature (GS) with clinical outcome in melanoma and non–small cell lung cancer (NSCLC) tumor samples from two phase III studies.

Experimental Design: The GS was prospectively validated using an adaptive signature design to optimize it for the sample type and technology used in phase III studies. One-third of the samples were used as “training set”; the remaining two thirds, constituting the “test set,” were used for the prospective validation of the GS.

Results: In the melanoma training set, the expression level of eight Th1/IFNγ-related genes in tumor-positive lymph node tissue predicted the duration of disease-free survival (DFS) and overall survival (OS) in the placebo arm. This GS was prospectively and independently validated as prognostic in the test set. Building a multivariate Cox model in the test set placebo patients from clinical covariates and the GS score, an increased number of melanoma-involved lymph nodes and the GS were associated with DFS and OS. This GS was not associated with DFS in NSCLC, although expression of the Th1/IFNγ-related genes was associated with the presence of lymphocytes in tumor samples in both indications.

Conclusions: These findings provide evidence that expression of Th1/IFNγ genes in the TME, as measured by this GS, is associated with clinical outcome in melanoma. This suggests that, using this GS, patients with stage IIIB/C melanoma can be classified into different risk groups.

Creators:
Creators
Email
Dizier, Benjamin
UNSPECIFIED
Callegaro, Andrea
UNSPECIFIED
Debois, Muriel
UNSPECIFIED
Dreno, Brigitte
UNSPECIFIED
Hersey, Peter
UNSPECIFIED
Gogas, Helen J.
UNSPECIFIED
Kirkwood, John M.
UNSPECIFIED
Vansteenkiste, Johan F.
UNSPECIFIED
Sequist, Lecia V.
UNSPECIFIED
Atanackovic, Djordje
UNSPECIFIED
Goeman, Jelle
UNSPECIFIED
van Houwelingen, Hans
UNSPECIFIED
Salceda, Susana
UNSPECIFIED
Wang, Fawn
UNSPECIFIED
Therasse, Patrick
UNSPECIFIED
Debruyne, Channa
UNSPECIFIED
Spiessens, Bart
UNSPECIFIED
Brichard, Vincent G.
UNSPECIFIED
Louahed, Jamila
UNSPECIFIED
Ulloa-Montoya, Fernando
UNSPECIFIED
Last Modified: 04 Jan 2021 01:21
URI: https://eprints.centenary.org.au/id/eprint/786

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