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Original Article | Open Access

High-precision immune-related plasma proteomics profiling predicts response to immunotherapy in patients with triple-negative breast cancer

Yuling Xiao1,*Hang Zhang1,*Yi Xiao1Ying Wang2Jing Zhang2Qi Hua2Pengchen Hu2Xinyan Lyu2Weihua Shou2Xin Hu1,3Zhiming Shao1Yizhou Jiang1 ( )Wei Huang2,3 ( )Jinxiu Shi2 ( )
Key Laboratory of Breast Cancer in Shanghai, Department of Breast Surgery, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
Shanghai-MOST Key Laboratory of Health and Disease Genomics, Shanghai Institute for Biomedical and Pharmaceutical Technologies (SIBPT), Shanghai 200237, China
Precision Cancer Medical Center Affiliated to Fudan University Shanghai Cancer Center, Shanghai 201315, China

*These authors contributed equally to this work.

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Abstract

Objective

While immunotherapy holds great potential for triple-negative breast cancer (TNBC), the lack of non-invasive biomarkers to identify beneficiaries limits the application.

Methods

Paired baseline, on-treatment, and post-treatment plasma samples were collected from 195 TNBC patients receiving anti-PD-1 immunotherapy in this retrospective study conducted at the Fudan University Shanghai Cancer Center (FUSCC) for sequential high-precision proteomic profiling.

Results

ARG1, NOS3, and CD28 were identified as plasma proteins significantly associated with the response to immunotherapy in neoadjuvant settings or in advanced stages of TNBC. Matched single-cell RNA sequencing data were incorporated to correlate peripheral plasma with the tumor microenvironment. Furthermore, the Plasma Immuno Prediction Score was developed to demonstrate significant predictive power for evaluating the efficacy and prognosis of patients undergoing neoadjuvant immunotherapy.

Conclusions

The results underscore the importance of systemic immunity in the immunotherapy response and support the use of plasma protein profiles as a feasible tool for enhancing personalized management of immunotherapy in breast cancer.

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Cancer Biology & Medicine
Pages 854-870

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Cite this article:
Xiao Y, Zhang H, Xiao Y, et al. High-precision immune-related plasma proteomics profiling predicts response to immunotherapy in patients with triple-negative breast cancer. Cancer Biology & Medicine, 2025, 22(7): 854-870. https://doi.org/10.20892/j.issn.2095-3941.2025.0038

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Received: 05 February 2025
Accepted: 20 May 2025
Published: 04 July 2025
©2025 The Authors.

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