Abstract PS4-01-16: The transcriptomic profile of circulating T lymphocytes is associated with response to neoadjuvant therapy in patients with early breast cancer

Abstract Background: In early breast cancer (eBC), anti-tumor immunity is a key determinant of response toneoadjuvant therapy (NAT). Immune profiling currently relies on static tissue biomarkers such astumor-infiltrating lymphocytes (TILs). However, the anti-tumor immune response is a dynamicprocess undergoing substantial changes during NAT. Compelling findings show that on-treatmentTILs are a stronger predictor of pCR than baseline TILs during NAT. Circulating immune cells mayoffer a non-invasive means to monitor systemic immune response during NAT. Here we present thepreliminary data for the development of a blood-based immune assay that analyzes transcriptomicdata from circulating immune cells. Methods. Baseline circulating T lymphocytes were collected from 95 eBC patients treated at ourinstitution between 2021–2023. The cohort included 39 HER2+ cases treated with NAT plus single(n=12) or dual HER2 blockade (n=27), 36 triple-negative cases treated with NAT alone (n=19) orNAT plus pembrolizumab (n=17), and 20 HR+/HER2- cases treated with anthracyclines-basedchemotherapy. Bulk RNA was extracted for gene expression analysis. 33 immune signatures werecalculated with known prognostic role in tumor tissue. Significant analysis of microarrays (SAM)was applied to identify differences in T cell polarization between the pCR and RD group. Results. 47 patients (49%) achieved pCR. The table below shows the genomic featuresdownregulated and upregulated in pCR. At SAM analysis, T cells of responders showed lowerexpression of genes linked to Tregs (FOXP3, CCR4), monocyte recruitment (CD163, IL1R2A), andsystemic inflammation (FGFR1, IL6R). A tissue-based gene signature associated to neutrophilactivation was upregulated in non-responders, along with chemokines linked to neutrophilrecruitment (CXCL8, CXCL2, CXCL1). Similarly, a tissue-based signature associated to IL6-JAK-STAT activation pathway was downregulated in T cells of responders. Conclusions. The transcriptomic profiling of T cells carries predictive information in eBC andreplicates the prognostic information captured by tissue-based signatures. This data supports thedevelopment of blood-based immune assays in eBC GENOMIC FEATURESlog2 FOLD CHANGEFALSE DISCOVERY RATECOX6CP1-0.542.09COL18A1-0.542.09CXCL8-0.502.09Neutrophil_Chemotaxis_NatureMed_20188-0.482.09S100A8-0.462.09S100A9-0.432.09FOXP3-0.422.09CCL4L2-0.402.09CXCL1-0.382.09CD163-0.382.09ITGA6-0.382.09CXCL2-0.372.09IGF1R-0.372.09BCL2-0.362.09CD14-0.362.09IL2RA-0.362.09CXCL3-0.332.09FGFR1-0.332.09COX7CP2-0.332.09PIM2-0.332.09CCDC154-0.322.09CCR2-0.312.09CD27-0.312.09IL6R-0.312.09IL6_JAK_STAT3_Pathway_GSEASig-0.292.09 Citation Format: B. Conte, S. D'Alfonso, M. Mellai, D. Cora, F. Favero, V. Martini, N. Negrini, I. Taglialatela, T. Landolfo, B. Ruffilli, S. Nardin, F. D'Avanzo, V. Rossi, C. Branni, M. Graeser, N. Harbeck, A. Gennari. The transcriptomic profile of circulating T lymphocytes is associated with response to neoadjuvant therapy in patients with early breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-01-16.