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Association of tumor-infiltrating lymphocyte subtypes with clinical characteristics and prognosis in young women with hormone receptor-positive breast cancer.

Association of tumor-infiltrating lymphocyte subtypes with clinical characteristics and prognosis in young women with hormone receptor-positive breast cancer. Clinical cancer research : an official journal of the American Association for Cancer Research Tesch, M. E., Zheng, Y., Guzman-Arocho, Y. D., Collins, L. C., Heng, Y. J., Tayob, N., Rosenberg, S. M., Ruddy, K. J., Tamimi, R. M., Schapira, L., Peppercorn, J., Borges, V., Come, S. E., Snow, C., Winer, E., Mittendorf, E. A., Partridge, A. H. 2025

Abstract

The role of tumor-infiltrating lymphocytes (TILs) remains unclear in hormone receptor (HR)-positive/HER2-negative breast cancer, particularly in young patients, whose immune microenvironment could be altered by age-related host and tumor differences.Patients with stage I-III HR-positive/HER2-negative tumors were identified from a prospective cohort study of breast cancer patients diagnosed at age = 40 years. Multiplexed immunofluorescence and semiautomated quantitative software measured cytotoxic T, non-CD8 T, T regulatory, exhausted T, and PDL1+ cells in stroma and tumor. Univariate analyses assessed differences in clinicopathologic characteristics by high versus low immune infiltration, divided based on median. TIL subtypes were evaluated as a continuous variable per 10% increase in Cox regression analyses for invasive breast cancer-free survival (iBCFS), distant disease-free survival (DDFS), and overall survival (OS), adjusted for clinicopathologic parameters.Among 390 patients, high immune infiltration was associated with increasing age, Black race, grade 3 tumors, and metaplastic or micropapillary histological subtypes. Over a median follow-up of 8 years, higher stromal and intratumoral non-CD8 T cell infiltration, T regulatory cell infiltration, and PDL1 expression was associated with improved iBCFS. Higher intratumoral non-CD8 T cell infiltration, T regulatory cell infiltration, and PDL1 expression was associated with improved DDFS; higher stromal PDL1 expression was also associated with improved DDFS. Higher intratumoral cytotoxic T cell infiltration and PDL1 expression was associated with improved OS.Characterization of immune subpopulations could help refine the prognostic value of TILs in young patients with HR-positive breast cancer, who may benefit from risk stratification for treatment individualization.

View details for DOI 10.1158/1078-0432.CCR-25-0948

View details for PubMedID 41117836