Programmed death-ligand 1 (PD-L1) is expressed in a significant number of the uterine cervical carcinomas

Abstract

BackgroundThe programmed death-1/programmed death-ligand-1 (PD-1/PD-L1) immune regulatory axis has emerged as a promising new target for cancer therapeutics, with lasting responses seen in the treatment of metastatic renal and lung carcinomas, as well as melanomas. As tumor surface expression of PD-L1 has been found to correlate with objective responses to anti-PD-L1 immunotherapies, we investigated the expression of PD-L1 in human cervical tumors and provide an adopted scoring system for the systematic evaluation of PD-L1 staining.MethodsImmunohistochemical staining for PD-L1 expression was performed on a tissue microarray of 101 normal and neoplastic cervical tissues. Neoplastic cores were divided into three groups: squamous cell carcinoma, adenosquamous carcinoma, and endocervical adenocarcinoma. PD-L1 expression was scored based on an adopted scoring system accounting to percentage and intensity of positivity, and results provided alongside available clinical and demographic data.ResultsOverall, PD-L1 was positive in 32 of 93 (34.4%) cervical carcinomas. Subcategorically, PD-L1 was positive in 28 of 74 (37.8%) squamous cell carcinomas, two of seven (28.6%) adenosquamous carcinomas, and two of 12 (16.7%) endocervical adenocarcinomas. It was negative in six benign cervical tissues.ConclusionsThis study shows a significant expression of PD-L1 in 34.4% of cervical carcinomas and no expression of PD-L1 in benign cervical tissues. These findings suggest a role for further investigation of anti-PD-L1/PD-1 immunotherapies in the treatment of PD-L1-positive cervical tumors. In addition, our adopted scoring system will facilitate more systematic correlations between tumor reactivity and response to treatment.

Efficacy and safety of nivolumab in Japanese patients with uterine cervical cancer, uterine corpus cancer, or soft tissue sarcoma: Multicenter, open‐label phase 2 trial

“…Clinical trials have shown antibodies against PD‐1 or PD‐L1 to be effective in blocking tumor immune evasion and inducing tumor regression in several types of cancer, including melanoma, non‐small cell lung cancer, and renal cell cancer . Some studies of PD‐L1 expression have reported PD‐L1 positivity in uterine cervical cancer, uterine corpus cancer, and STS, suggesting that these tumor types are potentially responsive to PD‐1/PD‐L1 blockade therapy. In support of this, the anti‐PD‐1 antibody pembrolizumab and the anti‐PD‐L1 antibody atezolizumab have shown antitumor activity in patients with uterine cervical cancer and/or patients with uterine corpus cancer …”

PD‐L1, RB1 and mismatch repair protein immunohistochemical expression in neuroendocrine carcinoma, small cell type, of the uterine cervix

“…[13][14][15][16] PD-L1 expression by tumour cells and/or tumourinfiltrating lymphocytes (TILs) and/or tumour-associated macrophages has been reported in several lower genital tract neoplasms, including cervical and vulvar squamous cell carcinoma, 13,[17][18][19][20] cervical squamous intraepithelial lesions, 20 cervical adenosquamous carcinoma 18 and endocervical adenocarcinoma. 18,19 A case of a PD-L1 negative SmCC-Cx with complete response to nivolumab (anti PD-1 therapeutic agent) was reported recently. 21 However, to our knowledge, the prevalence of PD-L1 expression in SmCC-Cx has not been systematically studied.…”

Immunotherapy for Uterine Cervical Cancer Using Checkpoint Inhibitors: Future Directions

“…Various researchers have also investigated PD-L1 expression in cervical cancer tissue. PD-L1 expression is observed in 34.4%-96% of cervical cancer tissues, but is rarely observed in histologically normal cervical tissue [15,16]. Analysis by histology type observed PD-L1 expression in 80% of cervical SCC [12].…”