Expression of programmed death-ligand 1, IRF1 and CD8 T lymphocyte infiltration in a primary subset of breast cancer patients in Sudan

Abstract

Objectives: This study aimed to investigate the protein expression of programmed death ligand 1 (PD-L1) in breast cancer (BC) tissues and link this data with estrogen status, the expression of interferon regulatory factor1 (IRF-1), and CD8þT lymphocyte infiltration by immunohistochemistry (IHC). We also attempted to identify the association between PD-L1 expression, the cell proliferation index marker (Ki67), and lymph node involvement. Methods: One hundred and fifty formalin-fixed and paraffin-embedded (FFPE) blocks of breast tissue were acquired from Sudanese females via The National Public Health Laboratory. FFPE blocks were subjected to antigen/ antibody detection by IHC with antibodies raised against PD-L1, IRF1, and CD8. These data were analyzed alongside data extracted from medical records relating to estrogen receptor (ER) status, Ki67 index, and lymph node (LN) status. Results: IHC analysis revealed a significant association between PD-L1 and CD8 (p ¼ 0.010). In addition, regression analysis indicated the ability of IRF1 to induce PD-L1 expression levels in IRF1-positive cases that were two-fold higher than IRF1-deficient cases (odds ratio [OR]: 2.441 p ¼ 0.035). Analysis also suggested that PDL1 exerts impact on cell proliferation, as reflected by the Ki67 index. An independent t test showed that higher Ki67 scores were more frequent among PD-L1-positive patients than in PD-L1-negative patients (t ¼ 2.608 p ¼ 0.014). There was an inverse association between PDL1 and ER status; ER-positive tumors exhibited negative PD-L1 expression and vice versa (p ¼ 0.04). Furthermore, we investigated the prognostic value of PD-L1 by evaluating the association between PD-L1 and LNs dispersed variably with tumor cells; there was no statistically significant relationship between these factors (p > 0.05). Conclusion: The expression of PD-L1 and IRF-1, along with the infiltration of CD8, represents a potent panel of biomarkers with which to identify BC patients with the highest probabilities of achieving an excellent response to immune therapy, particularly when taking ER status into account, as ER expression levels are known to be high when immune checkpoint blockers (ICBs) generate a poor response.