Metabolic Heterogeneity and Potential Immunotherapeutic Responses Revealed by Single-Cell Transcriptomics of Breast...

Area of Science:

• Oncology
• Genomics
• Cancer Research

Background:

• Breast cancer (BC) displays significant heterogeneity, but its transcriptomic landscape at the single-cell level remains incompletely understood.
• Elucidating BC heterogeneity is crucial for developing targeted therapies and improving patient outcomes.

Purpose of the Study:

• To comprehensively analyze the transcriptomic heterogeneity of breast cancer at the single-cell level.
• To investigate the relationship between cancer cell metabolism and chemotherapy resistance.
• To explore the potential of T-cell heterogeneity in predicting immunotherapy response.

Main Methods:

• Acquisition of breast cancer samples from 14 patients.
• Application of single-cell RNA sequencing (scRNA-seq) for transcriptomic profiling.
• Utilized bioinformatic analyses, immunohistochemistry (IHC), and immunofluorescence (IF) assays.

Main Results:

• Identified 10 distinct cell types, including Cancer-Associated Fibroblasts (CAFs) with functions potentially promoting therapy resistance.
• Revealed metabolic heterogeneity in tumor cells concerning glycolysis, gluconeogenesis, and fatty acid synthesis, correlating with chemotherapy resistance.
• Heterogeneity analysis of T cells and tumor cells suggested immunotherapy benefits for patients with multiple metastases and progression.

Conclusions:

• Provided a comprehensive understanding of breast cancer heterogeneity at the single-cell level.
• Established a link between cancer metabolism reprogramming and chemotherapy resistance.
• Enabled prediction of immunotherapy responses by analyzing T-cell heterogeneity.