Abstract P2-04-16: CD103+/PD-1+ T-cells identify a subset of triple-negative breast cancer eligible for targeted checkpoint inhibition
Authors: Bottai G , Loi S , Sotiriou C , Roncalli M , Pusztai L , Reis-Filho JS , Santarpia L 
Published: March 2017

Abstract
Background: The presence of tumor-infiltrating lymphocytes (TILs) is a prognostic factor in triple-negative breast cancer (TNBC). In particular, cytotoxic CD8+ cells are associated with favorable outcome in TNBC. Recently, the integrin CD103 have been suggested as a potential prognostic marker in a small cohort of triple-negative/basal-like breast cancer (Wang et al, Clin Cancer Res 2016). In this study, we aimed to evaluate the functional status and clinical relevance of CD8+ and CD103+ TILs in TNBC.
Methods: A large collection of formalin-fixed, paraffin-embedded tissues was retrospectively collected from 210 patients with primary invasive ductal TNBC. The presence of CD8, CD103 and the checkpoint receptor PD-1 was assessed by immunohistochemistry. Whole tumor slides were independently assessed by two pathologists blinded for patient characteristics and outcome. Cases where ≥5% of TILs expressed CD103 or PD-1 were considered positive. Statistical analyses were performed using Spearman's correlation, Kaplan-Meier and Cox regression analyses.
Results: We found that CD103+ cells mostly co-expressed the CD8 marker, and were preferentially distributed within tumor epithelium. No consistent correlation was found between the presence of CD103+ lymphocytes and the expression of its ligand E-cadherin by TNBC cells (rs=0.365). CD8+ lymphocytes were consistently associated with better relapse-free survival (RFS) and overall survival (OS) in both univariate (HR=0.61; P=1.06E-02 for RFS; HR=0.59; P=1.93E-02 for OS) and multivariate analysis (HR=0.65; P=2.45E-02 for RFS; HR=0.63; P=3.96E-02 for OS). The presence of CD103+ lymphocytes significantly correlated with prolonged RFS and OS in univariate analysis only (HR=0.82; P=4.12E-02 for RFS; HR=0.85; P=4.93E-02 for OS), and a trend for longer RFS was also observed in univariate analysis for PD-1 (HR=0.71; P=5.22E-02). Interestingly, a subset of TNBC showed co-expression of CD103+/PD-1+ in lymphocytes localized to the intraepithelial areas of the tumor.
Conclusions: The expression of CD103 on CD8+ T cells in direct contact with cancer cells may identify a subpopulation of cells with potent cytolytic activity. The interaction between CD103+ cytotoxic lymphocytes and cancer cells is mediated by mechanisms other than the binding to E-cadherin. Even though CD103 has a role in mediating an effective anti-tumor immune response, its presence alone may not be sufficient to impact the outcome of TNBC patients. Immunomodulatory therapies may be useful to boost the anti-tumor activity of potentially quiescent CD103+/PD-1+ cells in a subgroup of TNBC.
Citation Format: Bottai G, Loi S, Sotiriou C, Roncalli M, Pusztai L, Reis-Filho JS, Santarpia L. CD103+/PD-1+ T-cells identify a subset of triple-negative breast cancer eligible for targeted checkpoint inhibition [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-04-16.