Predictive and prognostic significance of CD8+ tumor-infiltrating lymphocytes in patients with luminal B/HER 2 negative breast cancer treated with neoadjuvant chemotherapy.

ABSTRACT

The immunobiology of breast cancer (BC) subtypes, including luminal cancer, remains unclear. Cluster of differentiation (CD)8+ tumor-infiltrating lymphocytes (TIL) are essential components of tumor-specific cellular adaptive immunity. However, only few studies have addressed the significance of cluster of differentiation 8+(CD8+) TIL in patients with luminal BC. The present study aimed to evaluate the predictive and prognostic significance of CD8+ TIL in patients with luminal B/human epidermal growth factor receptor 2 (HER 2)-negative BC treated with anthracycline-based neoadjuvant chemotherapy (NC). A total of 31 patients who underwent breast-conserving surgery or mastectomy post-NC were enrolled. Immunostaining for CD8+ TIL was performed using rabbit monoclonal antibodies against human CD8+. Intra- and peritumoral CD8+ TIL expression levels were classified into high and low, based on the median value of each. CD8+ TIL expression data were demonstrated to be correlated with disease-free survival (DFS) and overall survival (OS), using Kaplan-Meier and Cox's proportional hazards regression tests. The results revealed that, among all clinicopathological characteristics, only pathological complete response (pCR) was significantly correlated with intratumoral CD8+ TIL expression (P=0.016). A total of 9/16 patients (56%) with high intratumoral CD8+ TIL expression achieved pCR, in contrast with 2 out of 15 patients (13.3%) with low expression (P=0.016). High expression of intratumoral CD8+ TIL was significantly associated with OS (log-rank test, P=0.023). Multivariate Cox regression analysis revealed that intratumoral expression of CD8+ TIL was an independent prognostic factor for OS [hazard ratio (HR)=2.82; 95% confidence interval (CI)=0.911-4.833, P=0.007], but not for DFS (HR=1.11; 95% CI=0.282-2.078; P=0.508). In conclusion, the results of the present study suggested that high intratumoral CD8+ TIL expression was significantly predictive of pCR post-NC, and represented an independent prognostic factor for improved OS. In contrast, low intratumoral CD8+ TIL expression was a strong predictor of lack of pCR to NC, as well as an independent prognostic factor for poor OS. Assessment of the immune response in conjunction with the usual parameters may aid in the further stratification of patients with luminal B/HER 2-negative BC regarding the prediction of pCR post-NC and overall prognosis.