Cluster of differentiation 103 (CD103), also known as αEβ7 integrin, is expressed on subsets of CD8+ T lymphocytes and a biomarker for tissue resident memory CD8+ T cells (TRM). CD103 expression is upregulated upon antigen recognition concurrent with transforming growth factor β (TGFβ) stimulation. CD103 is primarily expressed in the intra-epithelial tumor-infiltrating lymphocytes (iTILs) compared with that in stromal TILs (sTILs). Here, we investigated the prognostic significance of CD103+ iTILs in invasive breast cancer (IBC). Immunohistochemistry was performed for CD103, TGFβ isoforms (1, 2, and 3), and TGFβ receptors on tissue microarrays of 1173 IBC samples. CD103 expression was analyzed using Aperio ScanScope slide scanner. An area with the highest density of CD103+ iTILs was captured at a magnification of × 200, and CD103+ iTILs per unit area (mm2) were enumerated. The threshold for CD103+ iTILs (high vs low) was determined based on the mean number. Immunohistochemical staining for TGFβ isoforms (1, 2, and 3) and their receptors was quantitated using H-score and calculated as: staining intensity (0-3) × the percentage of positive tumor cells (0-100%). For statistical analyses, we categorized cases as positive or negative based on the mean value of H-score. The number of CD103+ iTILs were compared with clinicopathological characteristics, and tumor cell expression of TGFβ and its receptors. Further, the relationship between CD103+ iTILs density and prognosis was investigated according to the molecular subtypes. CD103+ iTILs were observed in 713 (60.8%) cases with a mean ± standard deviation of 34.2 ± 94.6. Increased abundance of CD103+ iTILs was found to be significantly associated with histological grade 3, high Ki-67 labelling index, non-luminal subtypes, high sTIL density, and positive expression of TGFβ3 and its receptor (all, P< 0.001). Furthermore, high CD103+ iTIL density was significantly associated with prolonged overall survival (OS) (P = 0.02) and disease-free survival (DFS) (P = 0.001). Subgroup analysis according to molecular subtypes showed that CD103+ iTILs was prognostic only for triple-negative breast cancer (OS, P = 0.003; DFS, P = 0.005). Multivariate analysis of CD103+ iTILs with clinicopathological prognostic factors revealed that CD103+ iTILs was an independent prognostic factor for OS (P = 0.005) and DFS (P = 0.006) for the triple-negative subtype. Our study revealed that breast cancer cell expression of TGFβ3 may be involved in recruitment of CD103+ iTILs. In breast cancer, CD103+ iTILs indicates good prognosis which is an independent favorable prognostic factor in patients with triple negative subtype and more reliable than sTIL density.

Citation Format: Young Kyung Bae, Min Hui Park, Jung Eun Choi, Su Hwan Kang, Gyungyub Gong. Prognostic significance of intraepithelial CD103-positive tumor-infiltrating lymphocytes in breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-13.