Intratumoral CD103-positive tumour-infiltrating lymphocytes are associated with favourable prognosis in patients with triple-negative breast cancer

Abstract

Aims: Cluster of differentiation 103 (CD103), a marker of tissue resident memory T cells, is expressed on subsets of CD8+ T lymphocytes. We investigated the prognostic significance of CD103+ intra-epithelial tumour-infiltrating lymphocytes (iTILs) in invasive breast cancer (IBC).

Methods and results: Immunohistochemistry was performed for CD103, CD8 and TGF-β isoforms (1, 2 and 3) on tissue microarrays of 1187 IBC samples. CD103+ and CD8+ iTILs were present in 904 (76.2%) and 854 (74%) cases with an overall mean ± standard deviation of 38.2 ± 100.2/mm2 and 30.4 ± 89.7/mm2 , respectively. The numbers of CD103+ and CD8+ iTILs were positively correlated, and CD103+ iTILs outnumbered CD8+ iTILs in HER2-positive and triple-negative breast cancer (TNBC). CD103+ and CD8+ iTIL densities were significantly higher in tumours of histological grade 3, absence of lymphovascular invasion, high Ki-67 index, high stromal TIL density or TGF-β3 expression. High CD103+ iTIL density was associated with better disease-free survival (DFS, P = 0.007), but no significant association was observed for overall survival (OS). Subgroup analysis by cancer molecular subtype showed that CD103+ iTIL count was prognostic only for TNBC (OS, P = 0.035; DFS, P = 0.009). CD8+ iTIL density was significant for DFS, but not for OS, in the entire cohort and TNBC. In multivariate analysis, CD103+ iTIL density was an independent prognostic factor of OS (P = 0.02) and DFS (P = 0.007) in TNBC, while CD8+ iTIL density was not significant for survival.

Conclusions: CD103 iTIL density can serve as a predictor of good prognosis in patients with TNBC.