Dual Immunological Prognostic Models for Risk Stratification and Treatment Insights in Triple-Negative Breast Cancer.

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Triple-negative breast cancer (TNBC) is an aggressive subtype with a complex tumor microenvironment, hindering precise diagnosis and treatment.
• Understanding tumor-immune interactions is crucial for developing effective TNBC therapies.

Purpose of the Study:

• To develop a novel prognostic framework for TNBC based on tumor-immune interactions.
• To identify key molecular drivers and therapeutic targets within the TNBC microenvironment.

Main Methods:

• Integrative analysis of single-cell RNA sequencing data from 30 TNBC samples (106,132 cells).
• Identification of tumor expression metaprograms and their interaction with immunosuppressive dendritic cells via the NECTIN1-NECTIN4 axis.
• Development and validation of two prognostic models (SPSM and IPSM) using multi-cohort transcriptomic data.

Main Results:

• Two prognostic models, SPSM and IPSM, successfully stratified TNBC patients into distinct risk groups.
• Low-risk patients exhibited an immunologically active microenvironment and higher expression of immune checkpoint genes, indicating potential immunotherapy response.
• Identified imatinib and bortezomib as potential therapeutic agents.

Conclusions:

• The developed dual-model framework aids in TNBC risk stratification and offers insights for precision treatment.
• This research provides a foundation for understanding TNBC heterogeneity and developing novel therapeutic strategies, including immunotherapy.