Science et thérapie du cancer

The Prognostic Role of Tumor-Infiltrating Lymphocytes CD8 and Foxp3 and their Impact on Recurrence in Breast Cancer Patients

Abstract

Rasha Abd El-Ghany Khedr, Amr Abd El-Aziz Ghannam, Mohamed Ali El-Rashidy and Aliaa Atef Shama El-Deen

Background: The presence of tumor- infiltrating lymphocytes (TIL) within tumor epithelium or stroma of breast cancer is a surrogate of an immune response to cancer development, but their significance remains controversial. We conducted this study to evaluate the correlation of CD8+ (cytotoxic T) lymphocyte infiltration and Foxp3+ Tregs and tumor characteristics and their impact on recurrence in patients with invasive breast cancers.

Patients and methods: CD8+ T cells and Foxp3+ Tregs were detected by immunohistochemistry using the paraffin-embedded tumor tissues from 68 patients with stage (I to III) breast cancer. Clinicopathological data including patient’s age, tumor size and grade, stage, lymph node metastasis, estrogen and progesterone receptor status, Ki-67, and human epidermal growth factor receptor-2/neu, and recurrence were reviewed.

Results: The decreased mean number of CD8+ T cells was significantly associated with tumors with lymph node metastasis (P=0.02), and immune-positivity of Ki-67 (P=0.00). The increased number of Foxp3+ Tregs was significantly correlated with tumors with lymph node metastasis (P=0.01) higher stage (stage III, P=0.03), and immune-positivity for Ki-67 (P=0.02).

Further analysis of the correlation using CD8+ T-cell/Foxp3+ Treg ratio showed significant correlation with tumors with lymph node metastasis(P=0.01), and immune-positivity of Ki-67 (P=0.00). Also, there were significant correlations between the increased Foxp3+Treg /CD4+ T-cell ratio and lymph node metastasis (P=0.00), and immune-positivity of Ki-67 (P=0.02).

Conclusions: Data showed that lymph node metastases, tumor stage, immunopositivity of Ki67, and nontriple- negative tumors were associated with high regulatory T-cell infiltration. The prognostic role of immunologic balance as a marker for recurrence must be evaluated more clearly in a larger study.