CD8+ cytotoxic T cell and FOXP3+ regulatory T cell infiltration in relation to breast cancer survival and molecular subtypes
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The prognostic significance of tumor-associated FOXP3+ regulatory T cells (Tregs) and CD8+ cytotoxic T lymphocytes (CTLs) in invasive breast carcinomas is studied. Tregs and CTLs were assessed by immunohistochemistry in 1270 cases of invasive breast carcinoma for their associations with patient survival, histopathologic features, and molecular subtypes. Infiltrates of Tregs and CTLs were observed within tumor bed and in the tissue surrounding tumor. Within tumor bed, increased infiltration of Tregs and CTLs was significantly more common in those with unfavorable histologic features, including high histologic grade and negative ER and PR status. In addition, high density Treg infiltration was also associated with tumor HER2 overexpression, decreased overall survival (OS) and progression-free survival (PFS). In tissue surrounding tumor, in contrast, high CTL/Treg ratio was found to be significantly associated with improved OS and PFS. These prognostic associations were confirmed by multivariate analysis. Furthermore, the density of Treg infiltrates within tumors was inversely correlated with the prognosis of the molecular subtypes of tumors. The ratio of CTL/Treg infiltrates in the surrounding tissue was also significantly higher in luminal than non-luminal subtypes of carcinoma. The prognostic significances of Tregs and CTLs in breast carcinoma depend on their relative density and location. The density of intratumoral Treg infiltrates and the peritumoral CTL/Treg ratio are independent prognostic factors and correlated with the prognosis of the molecular subtypes of breast carcinoma, which may serve as potential target for stratifying immunotherapy to battle against the aggressive subtypes of breast carcinoma.
KeywordsBreast carcinoma Cytotoxic T cell Regulatory T cell Survival Molecular subtype
Research supported by grants from the National Natural Science Foundation of China (Grant No. 30930038), National “973” Program of China (Grant Nos. 2009CB521700; 2009CB918903) and the Program for Changjiang Scholars and Innovative Research Team in University (Grant No. IRT0743). We gratefully acknowledge Professor Wei Zheng, MD, PhD, Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt–Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA, for his criticism on reviewing the article.
Conflict of interest
No conflicts of interest were declared.