Dataset Information

Subsets of IFN Signaling Predict Response to Immune Checkpoint Blockade in Patients with Melanoma.

ABSTRACT:

Purpose

IFN signaling in the tumor microenvironment is a critical determinant of both response and resistance of cancer to immune checkpoint inhibitors (ICI). We hypothesized that distinct patterns of IFN signaling in melanoma are associated with clinical response or resistance to ICIs.

Experimental design

Two tissue microarrays containing samples from 97 patients with metastatic melanoma who received nivolumab, pembrolizumab, or a combination of ipilimumab and nivolumab at Yale New Haven Hospital between 2011 and 2017 were randomized into discovery and validation cohorts. Samples were stained and visualized using multiplexed immunofluorescence microscopy for STAT1, STAT1 phosphorylated at Y701 (pSTAT1Y701), and PD-L1, and signals were quantified using the automated quantitative analysis method of quantitative immunofluorescence. Treatment response was assessed using RECIST, and overall survival was analyzed. For in vitro studies, human melanoma cell lines were stimulated with IFNγ and IFNβ, and Western blotting was performed.

Results

Pretreatment STAT1 levels were higher in responders to ICIs [complete response/partial response/stable disease (SD) for > 6 months] than in nonresponders (SD < 6 months/progressive disease). Higher pretreatment STAT1 levels were associated with improved survival after ICIs in both the discovery and validation cohorts. Western blot analysis of human melanoma cell lines stimulated with IFN demonstrated distinct patterns of upregulation of STAT1 compared with pSTAT1Y701 and PD-L1. When combining STAT1 and PD-L1 markers, patients with STAT1highPD-L1low tumors had improved survival compared with those with STAT1lowPD-L1high tumors.

Conclusions

STAT1 may better predict melanoma response to ICIs than current strategies, and combined STAT1 and PD-L1 biomarkers may provide insight into IFN-responsive versus IFN-resistant states.

SUBMITTER: Horowitch B

PROVIDER: S-EPMC10524955 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

Subsets of IFN Signaling Predict Response to Immune Checkpoint Blockade in Patients with Melanoma.

Horowitch Brooke B Lee Daniel Y DY Ding Min M Martinez-Morilla Sandra S Aung Thazin Nwe TN Ouerghi Feriel F Wang Xueting X Wei Wei W Damsky William W Sznol Mario M Kluger Harriet H Rimm David L DL Ishizuka Jeffrey J JJ

Clinical cancer research : an official journal of the American Association for Cancer Research 20230801 15

<h4>Purpose</h4>IFN signaling in the tumor microenvironment is a critical determinant of both response and resistance of cancer to immune checkpoint inhibitors (ICI). We hypothesized that distinct patterns of IFN signaling in melanoma are associated with clinical response or resistance to ICIs.<h4>Experimental design</h4>Two tissue microarrays containing samples from 97 patients with metastatic melanoma who received nivolumab, pembrolizumab, or a combination of ipilimumab and nivolumab at Yale N ...[more]

PMID: 37233452

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Dataset Information

Subsets of IFN Signaling Predict Response to Immune Checkpoint Blockade in Patients with Melanoma.

Purpose

Experimental design

Results

Conclusions

Publications

Subsets of IFN Signaling Predict Response to Immune Checkpoint Blockade in Patients with Melanoma.

Similar Datasets

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