Comprehending the cuproptosis and cancer-immunity cycle network - delving into the immune landscape and its predictive role in breast cancer immunotherapy responses and clinical endpoints

Sep 21, 2026

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Role of cuproptosis, linked to tumor metabolism and immune recognition, remains insufficiently characterized within the cancer-immunity cycle (CIC) network. This study evaluates how the cuproptosis-CIC axis shapes immune responses and prognostic outcomes in breast cancer patients, and builds a comprehensive prediction framework. TCGA, GEO, and ICGC cohorts were integrated using CICs from the TIP database, with LASSO-Cox modeling and survival validation. Tumor microenvironment assessment used ESTIMATE and CIBERSORT, and key gene spatial patterns were explored by single-cell sequencing. Functional assays focused on cell survival and migration, identifying HSPA9 as a restraining factor with linked ceramide changes.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages19

Reading Time48 min

AccessFree to download

Introduction

Methods

Results

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Keywords

TYPE Original Research PUBLISHED 19 January 2024 DOI 10.3389/fimmu.2024.1344023 OPEN ACCESS EDITED BY Peixin Dong, Hokkaido University, Japan REVIEWED BY Kui Wang, Shanghai Jiao Tong University, China Chen Li, Free University of Berlin, Germany *CORRESPONDENCE Yanyu Qu [30342862@qq.com](30342862@qq.com) †These authors have contributed equally to this work RECEIVED 24 November 2023 ACCEPTED 02 January 2024 PUBLISHED 19 January 2024 CITATION Liu X, Xu F, Zhao K, Liu Y, Ye G, Zhang X and Qu Y (2024) Comprehending the cuproptosisand cancer-immunity cycle network: delving into the immune landscape and its predictive role in breast cancer immunotherapy responses and clinical endpoints. Front. Immunol. 15:1344023 . doi: 10.3389/fimmu.2024.1344023 COPYRIGHT © 2024 Liu, Xu, Zhao, Liu, Ye, Zhang and Qu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Comprehending the cuproptosisand cancer-immunity cycle network: delving into the immune landscape and its predictive role in breast cancer immunotherapy responsesand clinical endpoints Xiangwei Liu 1†, Feng Xu 2†, Kunkun Zhao 3†, Yunfei Liu 4, Guolin Ye 1, Xin Zhang 5 and Yanyu Qu 5* 1 Department of Breast Surgery, The First People’s Hospital of Foshan, Foshan, China, 2 Department of Anesthesiology, The First People ’s Hospital of Foshan, Foshan, China, 3 Department of Breast Surgery, Foresea Life Insurance Guangzhou General Hospital, Guangzhou, China, 4 Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany, 5 Department of Pathology, the Second People’s Hospital of Foshan, Foshan, China Background: The role of cuproptosis, a phenomenon associated with tumor metabolism and immunological identiﬁcation, remains underexplored, particularly in relation to the cancer-immunity cycle (CIC) network. This study aims to rigorously examine the impact of the cuproptosis-CIC nexus on immune reactions and prognostic outcomes in patients with breast cancer (BC), striving to establish a comprehensive prognostic model. Methods: In the study, we segregated data obtained from TCGA, GEO, and ICGC using CICs retrieved from the TIP database. We constructed a genetic prognostic framework using the LASSO-Cox model, followed by its validation through Cox proportional hazards regression. This framework’s validity was further conﬁrmed with data from ICGC and GEO. Explorations of the tumor microenvironment were carried out through the application of ESTIMATE and CIBERSORT algorithms, as well as machine learning techniques, to identify potential treatment strategies. Single-cell sequencing methods were utilized to delineate the spatial distribution of key genes within the various cell types in the tumor milieu. To explore the critical role of the identiﬁed CICs, experiments were conducted focusing on cell survival and migration abilities. Results: In our research, we identiﬁed a set of 4 crucial cuproptosis-CICs that have a profound impact on patient longevity and their response to immunotherapy. By leveraging these identiﬁed CICs, we constructed a predictive model that efﬁciently estimates patient prognoses. Detailed analyses at the single-cell level showed that the signiﬁcance of CICs. Experimental approaches, including CCK-8, Transwell, and wound healing assays, revealed that the protein HSPA9 restricts the growth and movement of breast cancer cells. Frontiers in Immunology 01 [frontiersin.org](frontiersin.org) Furthermore, our studies using immunoﬂuorescence techniques demonstrated that suppressing HSPA9 le

FAQs

What problem does the study address about cuproptosis and immune regulation in breast cancer?

It targets the limited understanding of how cuproptosis relates to the cancer-immunity cycle (CIC) network and how this connection affects immune reactions and outcomes in breast cancer.

How were the prognostic models constructed and validated?

Data from TCGA, GEO, and ICGC were integrated using CICs from TIP, followed by a LASSO-Cox genetic prognostic framework. Validation used Cox proportional hazards regression with additional ICGC and GEO data.

Which analytical tools were used to characterize the tumor microenvironment and gene distribution?

Tumor microenvironment infiltration was assessed with ESTIMATE and CIBERSORT, while single-cell sequencing was used to define the spatial distribution of key genes across tumor cell types.

Sep 21, 2026

Uploaded by Logic