title: The Role of PD-L1 Expression and Intratumoral Lymphocytes in Response to Perioperative Chemotherapy for Urothelial Carcinoma.
abstract: 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.
authors.affiliation: Institute for Pathology and Pathological Anatomy, Technische Universität München , Munich, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Erlmeier
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technische Universität München , Munich, Germany.
authors.forename: A K
authors.initials: AK
authors.lastname: Seitz
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technische Universität München , Munich, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Hatzichristodoulou
authors.affiliation: Institute for Medical Statistics and Epidemiology, Technische Universität München , Munich, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Stecher
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technische Universität München , Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Retz
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technische Universität München , Munich, Germany.
authors.forename: J E
authors.initials: JE
authors.lastname: Gschwend
authors.affiliation: Institute for Pathology and Pathological Anatomy, Technische Universität München, Munich, Germany; Member of the German Cancer Consortium (DKTK).
authors.forename: W
authors.initials: W
authors.lastname: Weichert
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technische Universität München , Munich, Germany.
authors.forename: H R
authors.initials: HR
authors.lastname: Kübler
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technische Universität München , Munich, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Horn
keywords: PD-L1; bladder cancer; perioperative chemotherapy