Evidence map›Paper›PMID 41044370›Full record

ArticleCommunications medicine2025

Predicting the response to immunotherapy from gene expression data in HER2-negative breast cancer.

Caterina A M La Porta, Ornella Garrone, Marco Merlano, Stefano Zapperi

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Article in Communications medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Caterina A M La Porta *Departement of Environmental Science and Policy, Center for Complexity and Biosystems, University of Milan, Milan, Italy. caterina.laporta@unimi.it.ORCID http://orcid.org/0000-0002-3010-8966
Ornella Garrone *Medical Oncology, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico di Milano, Milan, Italy.ORCID http://orcid.org/0000-0001-7359-5410
Marco MerlanoScientific Direction, Candiolo Cancer Institute, FPO-IRCCS Candiolo, Turin, Italy.
Stefano ZapperiDepartment of Physics, Center for Complexity and Biosystems, University of Milan, Milan, Italy.ORCID http://orcid.org/0000-0001-5692-5465

Funding

The I SPY 2.2 TRIAL: Evolving to Imaging and Molecular Biomarker Response Directed Adaptive Sequential Treatment to Optimize Breast Cancer OutcomesP01CA210961 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Nola M. Hylton-Watson · 2017 to 2026
$22.9M
Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research) 28402NCI NIH HHS P01 CA210961
6 · The paper itself

Abstract

backgroundThe addition of immunotherapy in the neoadjuvant setting is showing promising results for HER2- and triple-negative breast cancer patients, but pathological complete response is observed only in a fraction of patients. The aim of the present work was to investigate if ARIADNE, an algorithmic strategy to analyze gene expression data from bioptic samples based on epithelial-mesenchymal phenotypes, can predict the response to immunotherapy in HER2- patients.

methodsWe considered gene expression data for HER2-breast cancer patients treated with pembrolizumab in addition to chemotherapy (n = 69) and with chemotherapy alone (n = 179) from the I-SPY 2 trial. We stratified patients in two risk groups (low/high risk) according to the score of the ARIADNE algorithm and studied an additional cytokine signature. To better understand the significance of our results, we studied the interactions among genes in the PD-L1 pathway and analyzed single-cell data from TNBC patients treated with pembrolizumab.

resultsOur results show that ARIADNE predicts differential response to immunotherapy: the high-risk group has a pathological complete response (pCR) rate of 26% as compared with 62% for the low-risk group (OR 4.7, with 1.68-11.32 95% CI and p < 0.01). We also find significant correlations between a cytokine score and the rate of pCR. The ability of ARIADNE to predict pCR is associated with regulatory activity within the PD-L1 pathway. Comparison between ARIADNE and other immunological genomic signatures shows no correlations. The study of single-cell data showed that patients responding to immunotherapy display a larger number of exhausted T-cells than non-responders.

conclusionsOur analysis shows that ARIADNE is predictive of the response to immunotherapy, but not to chemotherapy, in HER2- patients.

Identifiers

PMID41044370
PMCPMC12494757

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