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Programmed death ligand 1 expression in prostate cancer cells is associated with deep changes of the tumor inflammatory infiltrate composition
Authors:Manuel Scimeca  Rita Bonfiglio  Nicoletta Urbano  Chiara Cerroni  Lucia Anemona  Manuela Montanaro  Sara Fazi  Orazio Schillaci  Alessandro Mauriello  Elena Bonanno
Affiliation:1. Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, Rome, Italy;2. San Raffaele University, Rome, Italy;3. OrchideaLab S.r.l., Rome, Italy;4. Department of Experimental Medicine and Surgery, University "Tor Vergata", Rome, Italy;5. Nuclear Medicine, Policlinico “Tor Vergata”, Rome, Italy;6. IRCCS Neuromed, Pozzilli, Italy;7. “Diagnostica Medica” and “Villa dei Platani”, Avellino, Italy
Abstract:

Background

The main aim of this study was to investigate the putative correlation between the composition of intratumoral inflammatory infiltrate and the expression of programmed death ligand 1 (PD-L1) by prostate cancer cells. In addition, we evaluated the correlation between the expression of PD-L1 and PTX3.

Methods

We enrolled 100 patients from which we collected one surgical sample each. Paraffin serial sections were obtained to perform histological classifications and tissues microarray construction. Serial tissues microarray paraffin sections were also used for PD-L1 analysis and intratumoral inflammatory infiltrate characterization (CD4, CD8, CD57, CD3, PD1, PSGL-1, TIGIT, CD20, CD38, CD68, CD163, and PTX3) by immunohistochemistry .

Results

Our result showed a significant increase of the number of both PD-L1 and PTX3 positive cells in prostate tumors respect to benign lesions. Inflammatory infiltrate of PD-L1 positive prostate cancer lesions was characterized by a decrease of both PD1 positive lymphocytes and tumor-infiltrated macrophages, mainly M2 subpopulation. Also, PTX3 expression showed an inverse correlation with the number of PD-L1 positive prostate cancer cells.

Conclusions

If confirmed, our data could be useful to predict the variations of the inflammatory population related to PD-L1 expression in prostate cancer. This can lay the foundation to establish therapeutic protocols able to inhibit the PD-L1 activity and, at the same time, to reactivate the antitumor inflammatory process.
Keywords:PD-L1  Cancer immune-escape  Prostate cancer  Macrophages  M2 polarization  PTX3
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