PD-L1 expression in cervical cancer tissue is strongly associated with the expression of CD73/TGF-β1, the percentage of CD8+/PD-1+ T cells and disease progression

The PD-1/PD-L1 signaling pathway plays a pivotal role in dampening anti-tumor immune responses. We previously reported that adenosine (Ado) increases the expression of programmed death ligand 1 (PD-L1) in cervical cancer (CC) cells by inducing TGF-β production. We also showed that supernatants from Ado-treated CC cells increased programmed cell death protein 1 (PD-1) expression in CD8+ T lymphocytes. In this study, we investigated the associations between PD-L1, CD73, and TGF-β expression and the percentage of PD-1-expressing CD8+ T lymphocytes in cervical tissue samples from normal donors (NDs), as well as patients with cervical intraepithelial neoplasia (CIN-I, CIN-II, CIN-III) and cervical cancer (CC). This retrospective observational study analyzed biopsies from untreated patients with CIN-1 (n = 27), CIN-II (n = 25), CIN-III (n = 23), and CC (n = 23), in addition to ND tissue samples (n = 30) as controls. Tissue microarrays (TMAs) were generated in triplicate and stained with anti-PD-L1, anti-CD73, anti-TGF-β1, anti-PD-1, and anti-CD8 monoclonal antibodies. Our results showed that the expression of PD-L1, CD73, and TGF-β1, along with the percentage of CD8+/PD-1 + T cells, increased in cervical tissues, correlating with disease progression. PD-L1 expression positively correlated with both CD73 (r = 0.8274, p < 0.001) and TGF-β1 (r = 0.8535, p < 0.001). Interestingly, the coexpression of PD-L1 and TGF-β1 in cervical tissues from patients with CIN-III and CC markedly increased. Furthermore, the percentage of CD8+ cells positively correlated with PD-1 expression (r = 0.7199, p < 0.01). These findings suggest that the expression of PD-L1 and PD-1 in CC tissues is strongly correlated with the expression of CD73 and TGF-β1. Therefore, the joint analysis of these biomarkers could be highly useful for evaluating disease prognosis and for developing strategies to improve the efficacy of immunotherapy protocols in CC patients treated with immune checkpoint inhibitors (ICIs).