Topic:
 
Issue Section:
 Biomarkers, translational research and precision medicine
Background: Ductal carcinoma in situ (DCIS) of the breast includes several subtypes with a divergent biological behavior. Data regarding the composition of DCIS-associated immune cells and their potential role in DCIS progression is limited. We studied DCIS-associated immune response by characterizing immune cell subsets according to DCIS subtypes.
Methods: DCIS-associated tumor infiltrating lymphocyte (TIL) density and distribution were evaluated based on H&E stained sections of excision specimens from 473 patients with DCIS. These cases were subtyped based on ER, PR and HER2. Patients were categorized as TIL-high or TIL-low. The DCIS-associated immune cells of TIL-high cases were immunostained on consecutive whole slides with CD4 (T-helper cells), CD8 (cytotoxic T-cells), CD20 (B-cells), CD68 (macrophages), FOXP3 (regulatory T-cells), PD-L1 (immune checkpoint ligand, clones SP142 and SP263).
Results: In total, 131/473 patients (27.7%) were considered as TIL-high and the percentage of TIL-high cases was significantly associated with DCIS subtype (11.4% of ER+PR+/-HER2-, 38.8% of ER+PR+/-HER2+, 61.2% of ER-PR-HER2+ and 63.6% of the TN subtype, P < 0.0001). There was no statistical difference in the immune cell composition according to DCIS subtypes. However, individual DCIS subtype comparison showed that the ER+PR+/-HER2+ subtype was associated with a significantly higher proportion of CD8+ T-cells compared to the TN subtype (P = 0.047). The ER-PR-HER2+ subtype was associated with a higher proportion of CD4+ T cells compared to the TN subtype, though significance was not reached (P = 0.061). PD-L1 expression by both clones was low. However, the mean value of PD-L1 SP263 was higher compared to PD-L1 SP142, for both TILs and tumor cells (P < 0.0001).
Conclusions: High numbers of TILs are mainly observed in HER+ and TN DCIS subtypes. The ER+ HER2+ DCIS subtype attracts more CD8+ T-cells compared to the TN subtype. This suggests a more pronounced anti-tumor immunity in HER2+ DCIS, which could play a role in its biological behavior.
Legal entity responsible for the study: Erasmus Medical Center Cancer Insitute, the Department of Pathology.
Funding: Roche.
Disclosure: All authors have declared no conflicts of interest.
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