Prognostic effect of different PD-L1 expression patterns in squamous cell carcinoma and adenocarcinoma of the cervix

Programmed death-ligand 1 (PD-L1) is expressed in various immune cells and tumor cells, and is able to bind to PD-1 on T lymphocytes, thereby inhibiting their function. At present, the PD-1/PD-L1 axis is a major immunotherapeutic target for checkpoint inhibition in various cancer types, but informat...

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Vydané v:	Modern pathology Ročník 29; číslo 7; s. 753 - 763
Hlavní autori:	Heeren, A Marijne, Punt, Simone, Bleeker, Maaike CG, Gaarenstroom, Katja N, van der Velden, Jacobus, Kenter, Gemma G, de Gruijl, Tanja D, Jordanova, Ekaterina S
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	New York Nature Publishing Group US 01.07.2016 Elsevier Limited Nature Publishing Group
Predmet:	13/51 631/67/327 631/67/580/1884 Adenocarcinoma - metabolism Adenocarcinoma - mortality Adenocarcinoma - pathology Adult Aged Aged, 80 and over B7-H1 Antigen - metabolism Biomarkers, Tumor - metabolism Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - mortality Carcinoma, Squamous Cell - pathology Cell death Cervical cancer Cervix Disease-Free Survival Female Gynecology Human papillomavirus Humans Immunohistochemistry Laboratory Medicine Ligands Lymphatic system Macrophages - metabolism Macrophages - pathology Medical prognosis Medicine Medicine & Public Health Metastasis Middle Aged Obstetrics Oncology Original original-article Pathology Patients Phenotype Prognosis Survival Rate Tumors Uterine Cervical Neoplasms - metabolism Uterine Cervical Neoplasms - mortality Uterine Cervical Neoplasms - pathology Young Adult Netherlands
ISSN:	0893-3952, 1530-0285, 1530-0285
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Shrnutí:	Programmed death-ligand 1 (PD-L1) is expressed in various immune cells and tumor cells, and is able to bind to PD-1 on T lymphocytes, thereby inhibiting their function. At present, the PD-1/PD-L1 axis is a major immunotherapeutic target for checkpoint inhibition in various cancer types, but information on the clinical significance of PD-L1 expression in cervical cancer is largely lacking. Here, we studied PD-L1 expression in paraffin-embedded samples from two cohorts of patients with cervical cancer: primary tumor samples from cohort I (squamous cell carcinoma, n =156 and adenocarcinoma, n =49) and primary and paired metastatic tumor samples from cohort II (squamous cell carcinoma, n =96 and adenocarcinoma, n =31). Squamous cell carcinomas were more frequently positive for PD-L1 and also contained more PD-L1-positive tumor-associated macrophages as compared with adenocarcinomas (both P <0.001). PD-L1-positive tumor-associated macrophages were found to express CD163 and/or CD14 by triple fluorescent immunohistochemistry, demonstrating an M2-like phenotype. Interestingly, disease-free survival ( P =0.022) and disease-specific survival ( P =0.046) were significantly poorer in squamous cell carcinoma patients with diffuse PD-L1 expression as compared with patients with marginal PD-L1 expression (i.e., on the interface between tumor and stroma) in primary tumors. Disease-specific survival was significantly worse in adenocarcinoma patients with PD-L1-positive tumor-associated macrophages compared with adenocarcinoma patients without PD-L1-positive tumor-associated macrophages ( P =0.014). No differences in PD-L1 expression between primary tumors and paired metastatic lymph nodes were detected. However, PD-L1-positive immune cells were found in greater abundance around the metastatic tumors as compared with the paired primary tumors ( P =0.001 for squamous cell carcinoma and P =0.041 for adenocarcinoma). These findings point to a key role of PD-L1 in immune escape of cervical cancer, and provide a rationale for therapeutic targeting of the PD-1/PD-L1 pathway.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0893-3952 1530-0285 1530-0285
DOI:	10.1038/modpathol.2016.64