Functional CD3+CD8+PD1- T Cell Accumulation and PD-L1 Expression Increases During Tumor Invasion in DCIS of the Breast

Abstract

Background: The changes in T cell subsets and programmed death ligand 1 (PD-L1) expression during the transition from ductal carcinoma in situ (DCIS) to early invasive breast cancer had not been well studied.

Patients and methods: A total of 85 DCIS patients were classified into 49 DCIS (clinical stage: Tis, noninvasive) and 36 with a minimally infiltrating lesion (MIL; < 5 mm; clinical stage: T1a). We explored the quantitative alterations of T-cell markers and PD-L1 in these groups using the Opal multi-immunohistochemistry technique.

Results: We observed increased infiltration of CD3-positive (CD3⁺)CD8⁺ programmed death 1 (PD1)-negative T cells and higher PD-L1 expression in DCIS with MIL. Elevated PD1 expression correlated with PD-L1 expression in MIL and DCIS.

Conclusion: We conclude that during the transition from DCIS to an invasive lesion, the host cytolytic T cells begin interacting with the tumor and destroy the tumor tissue, leading to an adaptive upregulation of PD-L1 and tumor protection against immune destruction.

Keywords: Breast cancer; Immune phenotype; Opal technique; PD1 immune microenvironment; T cells expression.