T-cell activation profiles predict outcomes of neoadjuvant therapy in breast cancer.

Authors

Chaoni Cai, Jialing Huang, Jinfeng Li, Saixiang Zheng, Dijin Lin, Chaohui Duan, Ying Xu

Published in

Clinical immunology (Orlando, Fla.). Pages 110762. Aug 20, 2026. Epub Aug 20, 2026.

Abstract

Peripheral blood T-cell monitoring may predict treatment response and recurrence in breast cancer patients receiving neoadjuvant therapy (NAT).
The retrospective, single-center study enrolled 210 primary breast cancer patients (2020-2024). Peripheral T-cell subsets (CD69⁺, HLA-DR⁺, etc.) and tumor markers (CEA, CA125, etc.) were assessed at baseline, post-NAT, and post-surgery. Receiver operating characteristic (ROC) curves, Logistic and Cox regression, decision curve analysis, longitudinal trajectory analysis, and Gene Set Enrichment Analysis (GSEA) were performed.
Baseline CD3⁺CD69⁺T /CD3⁺T and CD3⁺HLA-DR⁺T /CD3⁺T ratios independently predicted pathological complete response (pCR) with a combined AUC of 0.87. Post-NAT Treg /CD4⁺T and CD3⁺HLA-DR⁺T /CD3⁺T predicted recurrence/metastasis (AUC = 0.85). Post-surgery, the combination of CD3⁺CD8⁺HLA-DR⁺T /CD3⁺T and CA125 achieved an AUC of 0.88. Post-treatment T-cell activation correlated with improved survival. Three-year trajectory analysis revealed distinct T-cell dynamics between no recurrence/metastasis and recurrence/metastasis patients. GSEA showed CD69-high CD8⁺T were enriched in inflammatory pathways, whereas HLA-DR-high CD8⁺T were enriched in cell-cycle, metabolism, and effector pathways.
Peripheral T-cell activation profiles were associated with NAT response and clinical outcomes in this cohort, suggesting their potential as dynamic biomarkers for recurrence/metastasis risk stratification. However, given the retrospective, single-center design and lack of external validation, these internally validated models warrant independent prospective validation prior to clinical application.

PMID:
42624273
Bibliographic data and abstract were imported from PubMed on 21 Aug 2026.

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