Cargando…
The Role of PD-L1 Expression and Intratumoral Lymphocytes in Response to Perioperative Chemotherapy for Urothelial Carcinoma
Introduction: Immunological pathways are relevant for the effectiveness of conventional cytotoxic chemotherapy. Recently, checkpoint inhibition of the PD-1/PD-L1 axis has been shown to be therapeutically relevant in urothelial carcinoma. Objective: To monitor PD-L1 expression on tumor cells and intr...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
IOS Press
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5181663/ https://www.ncbi.nlm.nih.gov/pubmed/28035323 http://dx.doi.org/10.3233/BLC-160067 |
_version_ | 1782485742441725952 |
---|---|
author | Erlmeier, F. Seitz, A.K. Hatzichristodoulou, G. Stecher, L. Retz, M. Gschwend, J.E. Weichert, W. Kübler, H.R. Horn, T. |
author_facet | Erlmeier, F. Seitz, A.K. Hatzichristodoulou, G. Stecher, L. Retz, M. Gschwend, J.E. Weichert, W. Kübler, H.R. Horn, T. |
author_sort | Erlmeier, F. |
collection | PubMed |
description | Introduction: Immunological pathways are relevant for the effectiveness of conventional cytotoxic chemotherapy. Recently, checkpoint inhibition of the PD-1/PD-L1 axis has been shown to be therapeutically relevant in urothelial carcinoma. Objective: To monitor PD-L1 expression on tumor cells and intratumoral infiltration with CD8 positive lymphocytes during perioperative chemotherapy for urothelial cancer and to evaluate their use as potential predictive markers for chemotherapy. Patients and Methods: Sixty-four patients with muscle-invasive urothelial cancer were included in the analysis. Twenty-two patients received preoperative chemotherapy and 42 were treated in an adjuvant setting for locally advanced disease or lymph node metastases. PD-L1 status and the density of infiltration with CD8-positive cells were assessed by immunohistochemistry and analysed for their association with survival (adjuvant group) and response to chemotherapy (preoperative group). For PD-L1 positivity we used a cutoff of 10% positive tumor cells. Results: In the adjuvant group, 11 of 42 patients (26.2%) had PD-L1 positive tumor cells. Twenty-six of 42 (61.9%) patients were highly infiltrated with CD8 + lymphocytes. There was no significant evidence of an association with overall survival for PD-L1 status nor for CD8 infiltration density (p = 0.63 and 0.71). In the preoperative group, eight of the 22 (36.4%) patients were PD-L1 positive and 13 (59%) were highly infiltrated with CD8 + lymphocytes before chemotherapy. There was no evidence of associations with response or survival. Eight patients showed a pathological response to preoperative treatment. These had a significantly longer overall survival than non-responders (p = 0.01). In the preoperative group the pre-treatment expression of the immunologic markers could be compared to the post-treatment status. Only one patient showed a changed PD-L1 status and three patients a changed CD8 status. Conclusions: The tumoral expression of PD-L1 in urothelial carcinoma does not seem to be largely influenced by chemotherapy. Our data do not provide evidence that tumoral expression of PD-L1 and CD8 are useful as prognostic or predictive markers. Small sample size is the major limitation of our study. |
format | Online Article Text |
id | pubmed-5181663 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | IOS Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-51816632016-12-27 The Role of PD-L1 Expression and Intratumoral Lymphocytes in Response to Perioperative Chemotherapy for Urothelial Carcinoma Erlmeier, F. Seitz, A.K. Hatzichristodoulou, G. Stecher, L. Retz, M. Gschwend, J.E. Weichert, W. Kübler, H.R. Horn, T. Bladder Cancer Research Report Introduction: Immunological pathways are relevant for the effectiveness of conventional cytotoxic chemotherapy. Recently, checkpoint inhibition of the PD-1/PD-L1 axis has been shown to be therapeutically relevant in urothelial carcinoma. Objective: To monitor PD-L1 expression on tumor cells and intratumoral infiltration with CD8 positive lymphocytes during perioperative chemotherapy for urothelial cancer and to evaluate their use as potential predictive markers for chemotherapy. Patients and Methods: Sixty-four patients with muscle-invasive urothelial cancer were included in the analysis. Twenty-two patients received preoperative chemotherapy and 42 were treated in an adjuvant setting for locally advanced disease or lymph node metastases. PD-L1 status and the density of infiltration with CD8-positive cells were assessed by immunohistochemistry and analysed for their association with survival (adjuvant group) and response to chemotherapy (preoperative group). For PD-L1 positivity we used a cutoff of 10% positive tumor cells. Results: In the adjuvant group, 11 of 42 patients (26.2%) had PD-L1 positive tumor cells. Twenty-six of 42 (61.9%) patients were highly infiltrated with CD8 + lymphocytes. There was no significant evidence of an association with overall survival for PD-L1 status nor for CD8 infiltration density (p = 0.63 and 0.71). In the preoperative group, eight of the 22 (36.4%) patients were PD-L1 positive and 13 (59%) were highly infiltrated with CD8 + lymphocytes before chemotherapy. There was no evidence of associations with response or survival. Eight patients showed a pathological response to preoperative treatment. These had a significantly longer overall survival than non-responders (p = 0.01). In the preoperative group the pre-treatment expression of the immunologic markers could be compared to the post-treatment status. Only one patient showed a changed PD-L1 status and three patients a changed CD8 status. Conclusions: The tumoral expression of PD-L1 in urothelial carcinoma does not seem to be largely influenced by chemotherapy. Our data do not provide evidence that tumoral expression of PD-L1 and CD8 are useful as prognostic or predictive markers. Small sample size is the major limitation of our study. IOS Press 2016-10-27 /pmc/articles/PMC5181663/ /pubmed/28035323 http://dx.doi.org/10.3233/BLC-160067 Text en IOS Press and the authors. All rights reserved https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) License (https://creativecommons.org/licenses/by-nc/4.0/) , which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Report Erlmeier, F. Seitz, A.K. Hatzichristodoulou, G. Stecher, L. Retz, M. Gschwend, J.E. Weichert, W. Kübler, H.R. Horn, T. The Role of PD-L1 Expression and Intratumoral Lymphocytes in Response to Perioperative Chemotherapy for Urothelial Carcinoma |
title | The Role of PD-L1 Expression and Intratumoral Lymphocytes in Response to Perioperative Chemotherapy for Urothelial Carcinoma |
title_full | The Role of PD-L1 Expression and Intratumoral Lymphocytes in Response to Perioperative Chemotherapy for Urothelial Carcinoma |
title_fullStr | The Role of PD-L1 Expression and Intratumoral Lymphocytes in Response to Perioperative Chemotherapy for Urothelial Carcinoma |
title_full_unstemmed | The Role of PD-L1 Expression and Intratumoral Lymphocytes in Response to Perioperative Chemotherapy for Urothelial Carcinoma |
title_short | The Role of PD-L1 Expression and Intratumoral Lymphocytes in Response to Perioperative Chemotherapy for Urothelial Carcinoma |
title_sort | role of pd-l1 expression and intratumoral lymphocytes in response to perioperative chemotherapy for urothelial carcinoma |
topic | Research Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5181663/ https://www.ncbi.nlm.nih.gov/pubmed/28035323 http://dx.doi.org/10.3233/BLC-160067 |
work_keys_str_mv | AT erlmeierf theroleofpdl1expressionandintratumorallymphocytesinresponsetoperioperativechemotherapyforurothelialcarcinoma AT seitzak theroleofpdl1expressionandintratumorallymphocytesinresponsetoperioperativechemotherapyforurothelialcarcinoma AT hatzichristodouloug theroleofpdl1expressionandintratumorallymphocytesinresponsetoperioperativechemotherapyforurothelialcarcinoma AT stecherl theroleofpdl1expressionandintratumorallymphocytesinresponsetoperioperativechemotherapyforurothelialcarcinoma AT retzm theroleofpdl1expressionandintratumorallymphocytesinresponsetoperioperativechemotherapyforurothelialcarcinoma AT gschwendje theroleofpdl1expressionandintratumorallymphocytesinresponsetoperioperativechemotherapyforurothelialcarcinoma AT weichertw theroleofpdl1expressionandintratumorallymphocytesinresponsetoperioperativechemotherapyforurothelialcarcinoma AT kublerhr theroleofpdl1expressionandintratumorallymphocytesinresponsetoperioperativechemotherapyforurothelialcarcinoma AT hornt theroleofpdl1expressionandintratumorallymphocytesinresponsetoperioperativechemotherapyforurothelialcarcinoma AT erlmeierf roleofpdl1expressionandintratumorallymphocytesinresponsetoperioperativechemotherapyforurothelialcarcinoma AT seitzak roleofpdl1expressionandintratumorallymphocytesinresponsetoperioperativechemotherapyforurothelialcarcinoma AT hatzichristodouloug roleofpdl1expressionandintratumorallymphocytesinresponsetoperioperativechemotherapyforurothelialcarcinoma AT stecherl roleofpdl1expressionandintratumorallymphocytesinresponsetoperioperativechemotherapyforurothelialcarcinoma AT retzm roleofpdl1expressionandintratumorallymphocytesinresponsetoperioperativechemotherapyforurothelialcarcinoma AT gschwendje roleofpdl1expressionandintratumorallymphocytesinresponsetoperioperativechemotherapyforurothelialcarcinoma AT weichertw roleofpdl1expressionandintratumorallymphocytesinresponsetoperioperativechemotherapyforurothelialcarcinoma AT kublerhr roleofpdl1expressionandintratumorallymphocytesinresponsetoperioperativechemotherapyforurothelialcarcinoma AT hornt roleofpdl1expressionandintratumorallymphocytesinresponsetoperioperativechemotherapyforurothelialcarcinoma |