# Peripheral blood gene expression signatures of systemic immunity predict tumor microenvironment biology and therapeutic response in breast cancer

## TL;DR

This study shows that gene expression in blood can predict how breast cancer patients will respond to immunotherapy, offering a non-invasive way to guide treatment.

## Contribution

The novel contribution is the identification of peripheral blood gene expression signatures that predict tumor microenvironment biology and immunotherapy response in breast cancer.

## Key findings

- Triple negative breast cancer patients showed higher T cell receptor clonality and immune activation signatures.
- A logistic regression model based on immune features predicted response to pembrolizumab and was validated in a dostarlimab-treated cohort.

## Abstract

This study investigates the association between peripheral blood immunological features and immunotherapy response in breast cancer. We generated and analyzed RNAseq data from 546 blood samples of patients with high-risk stage II/III HER2-negative breast cancer enrolled in the I-SPY2 trial and identified peripheral immune signatures associated with tumor characteristics and immunotherapy response. Triple negative breast cancer (TNBC) patients showed higher T cell receptor (TCR) clonality and immune activation signatures. Responders to the chemotherapy + pembrolizumab regimen had high baseline TCR diversity, with TNBC responders experiencing T cell clonal expansion and activation after treatment. A logistic regression model based on immunological features before and early-on-treatment predicted response to pembrolizumab. The model was validated in an independent cohort of patients treated with dostarlimab in the neoadjuvant setting. We report the potential of peripheral blood-derived gene expression tests to predict immunotherapy benefit, guiding personalized treatment in breast cancer with a minimally invasive approach.