The presence of tumor-infiltrating lymphocytes (TILs) is a prognostic factor in triple-negative breast cancer (TNBC). Specifically, cytotoxic CD8+ cells are associated with favorable outcome in TNBC. Recently, the integrin CD103 has been suggested as a potential prognostic marker in breast cancer. In this study, we aimed to evaluate the functional status and clinical relevance of CD8+ and CD103+ TILs in TNBC.
A retrospective cohort of 210 formalin-fixed, paraffin-embedded tissues from patients with primary invasive ductal TNBC was assessed for the presence of CD8, CD103 and the checkpoint receptor PD-1 by immunohistochemistry assay. Whole tumor slides were assessed. 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.
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.
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 TNBC cells is mediated by different mechanisms rather 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 patients.
Citation Format: Giulia Bottai, Massimo Roncalli, Libero Santarpia. CD103+/PD-1+ T-cells identify a subset of triple-negative breast cancer eligible for targeted checkpoint inhibition [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A118.
- ©2016 American Association for Cancer Research.