Longitudinal tissue analysis reveals microenvironmental changes correlate with combined immunotherapy and targeted therapy response in metastatic breast cancer

Jian-You Liao ^1,2, Jien Wang ¹, Hengyu Li ³

¹Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
²Center for Precision Medicine, Shenshan Central Hospital, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Shenwei, People's Republic of China.
³Department of Breast and Thyroid Surgery, Naval Military Medical University, Shanghai, China.
⁴Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
⁵Department of Breast Surgery, Fujian Cancer Hospital, Fuzhou, China.
⁶Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
⁷Jiangsu Alphamab Biopharmaceuticals Co.,Ltd, Suzhou, People's Republic of China.
⁸Department of Breast Surgery, Fujian Cancer Hospital, Fuzhou, China liujieqiong01@163.com songcg1971@hotmail.com.
⁹Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China liujieqiong01@163.com songcg1971@hotmail.com.

⁰Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Journal for Immunotherapy of Cancer +

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October 6, 2025

View abstract on PubMed

Summary

Longitudinal tumor microenvironment (TME) multi-omics analysis reveals immune cell shifts linked to treatment response in metastatic breast cancer. Understanding these TME dynamics offers clinical value for evaluating therapeutic effectiveness.

Area Of Science

Oncology
Immunology
Genomics

Background

Interrogating the tumor microenvironment (TME) is crucial for understanding treatment response and disease progression.
Longitudinal tissue analysis and multi-omics integration present challenges but hold potential value in clinical settings.

Purpose Of The Study

To investigate the impact of a novel bispecific antibody combination therapy on the TME in treatment-resistant metastatic breast cancer.
To define the value of longitudinal biopsies integrated with multi-omics analyses.

Main Methods

Conducted a multicenter phase 2 clinical trial for metastatic breast cancer.
Performed longitudinal tumor tissue sampling before and after treatment.
Utilized single-cell RNA and T cell receptor sequencing on 334,183 cells.

Main Results

Observed significant temporal shifts in immune cell populations and phenotypes within the TME correlating with treatment responses.
Found activation of regulatory T cells and depletion of effector T cells, NK cells, and dendritic cells in non-responding tumors.
Demonstrated temporal shifts in immune cell populations and phenotypes within the TME.

Conclusions

Longitudinal TME multi-omics analysis provides valuable insights into disease processes.
This approach can enhance the clinical evaluation of treatment responses in metastatic breast cancer.

Keywords:

Breast Cancer Combination therapy Immunotherapy Tumor microenvironment - TME

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