Journal
JOURNAL OF TAIBAH UNIVERSITY MEDICAL SCIENCES
Volume 19, Issue 1, Pages 99-105Publisher
ELSEVIER
DOI: 10.1016/j.jtumed.2023.08.006
Keywords
Breast cancer; CD8 infiltration; ER; Immunotherapy; IRF1; PD-L1
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This study investigated the protein expression of PD-L1 in breast cancer tissues and its association with estrogen status, IRF-1 expression, and CD8 T lymphocyte infiltration. The results showed a significant association between PD-L1 and CD8, and IRF-1 was found to induce higher levels of PD-L1 expression. PD-L1 was also found to impact cell proliferation, as reflected by the Ki67 index. There was an inverse association between PD-L1 and ER status. The findings suggest that PD-L1, along with IRF-1 and CD8, could serve as potential biomarkers for predicting immune therapy response in breast cancer patients.
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 CD8 thorn T lymphocyte infiltration by immu-nohistochemistry (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 = 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 = 0.035). Analysis also suggested that PD-L1 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 = 2.608 p = 0.014). There was an inverse association between PD-L1 and ER status; ER-positive tumors exhibited negative PD-L1 expression and vice versa (p = 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.
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