Erlmeier F, Seitz A K, Hatzichristodoulou G, Stecher L, Retz M, Gschwend J E, Weichert W, Kübler H R, Horn T
Institute for Pathology and Pathological Anatomy, Technische Universität München , Munich, Germany.
Department of Urology, Klinikum rechts der Isar, Technische Universität München , Munich, Germany.
Bladder Cancer. 2016 Oct 27;2(4):425-432. doi: 10.3233/BLC-160067.
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. 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. 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. 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 ( = 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 ( = 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. 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.
免疫途径与传统细胞毒性化疗的疗效相关。最近，PD-1/PD-L1轴的检查点抑制已被证明在尿路上皮癌的治疗中具有相关性。目的是监测尿路上皮癌围手术期化疗期间肿瘤细胞上的PD-L1表达以及肿瘤内CD8阳性淋巴细胞浸润情况，并评估它们作为化疗潜在预测标志物的用途。64例肌层浸润性尿路上皮癌患者纳入分析。22例患者接受术前化疗，42例因局部晚期疾病或淋巴结转移接受辅助治疗。通过免疫组织化学评估PD-L1状态和CD8阳性细胞浸润密度，并分析它们与生存（辅助组）和化疗反应（术前组）的相关性。对于PD-L1阳性，我们使用10%阳性肿瘤细胞的临界值。在辅助组中，42例患者中有11例（26.2%）肿瘤细胞PD-L1阳性。42例患者中有26例（61.9%）CD8 +淋巴细胞高度浸润。PD-L1状态和CD8浸润密度与总生存无显著相关性证据（P = 0.63和0.71）。在术前组中，22例患者中有8例（36.4%）化疗前PD-L1阳性，13例（59%）CD8 +淋巴细胞高度浸润。无证据表明与反应或生存相关。8例患者对术前治疗有病理反应。这些患者的总生存明显长于无反应者（P = 0.01）。在术前组中，可将免疫标志物的治疗前表达与治疗后状态进行比较。仅1例患者PD-L1状态改变，3例患者CD8状态改变。尿路上皮癌中PD-L1的肿瘤表达似乎在很大程度上不受化疗影响。我们的数据未提供证据表明PD-L1和CD8的肿瘤表达可作为预后或预测标志物。小样本量是我们研究的主要局限性。
