Peripheral blood gene expression signatures of systemic immunity predict tumor microenvironment biology and therapeutic response in breast cancer
Year: 2025
Type: preprint
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.
Source: Research Square
Authors: Justin Balko, Xiaopeng Sun, Ann Hanna, Andres Ocampo, Brandie Taylor, Jacey Marshall, Julia Steele, Margaret Axelrod, Elizabeth Wescott, Susan Opalenik, Angela DeMichele, Laura Esserman, Minetta Liu, Rita Nanda, Denise Wolf, Lamorna Brown Swigart, Gillian Hirst, Laura Van 'T Veer, Yaomin Xu
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: U.S. Department of Defense, Breast Cancer Research Foundation, AstraZeneca, Gilead Sciences, American Society of Clinical Oncology, Vanderbilt University, Vanderbilt-Ingram Cancer Center, Genomic Health, Menarini Silicon Biosystems, Natera, Eisai, National Institutes of Health, Genentech, National Cancer Institute
Awards: G1300984159, G2477219477, G2668464526, G275963511, G3238356313, G3433274139, G4510989636, G4513176822, G5853943267, G6632558474, SPORE in Breast Cancer, G9000081609, The Cancer Cell Map Initiative v2.0, Cancer Center Support Grant, Cancer Center Support Grant, The I SPY 2.2 TRIAL: Evolving to Imaging and Molecular Biomarker Response Directed Adaptive Sequential Treatment to Optimize Breast Cancer Outcomes, Strategy for combining circulating tumor DNA (ctDNA) and magnetic resonance imaging (MRI) measures of tumor burden for prediction of response and outcome in neoadjuvant-treated early breast cancer
OpenAlex ID: W4412095090