非常规 T 细胞在泌尿系统肿瘤中：能抓住就抓住
Unconventional T cells in urological cancers: catch them if you can.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
STAT3、PD-L1 和 PD-L2 在 BCG 治疗前后 Ta/T1 尿路上皮癌中表达的预后价值
英文原题：The prognostic value of expressions of STAT3, PD-L1, and PD-L2 in Ta/T1 urothelial carcinoma before and after BCG treatment.
查看英文原题
The prognostic value of expressions of STAT3, PD-L1, and PD-L2 in Ta/T1 urothelial carcinoma before and after BCG treatment.
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研究概要
BCG 治疗在 NMIBC 中的成功与 PD-L1、PD-L2 和 STAT3 表达状态无关，但 PD-L1 表达与 PD-L2、STAT3 以及 TILs 率均相关，然而这种相关性在 BCG 治疗后消失。
研究思路结论见上方概要
背景
非肌层浸润性膀胱癌（NMIBC）是老年人和男性中常见的诊断肿瘤（中位年龄：69岁）。免疫治疗是对卡介苗（BCG）治疗耐药病例的一种治疗选择。我们旨在评估与免疫机制密切相关的程序性细胞死亡配体（PD-L）-1（PD-L1）、PD-L2和信号转导及转录激活因子3（STAT3）表达在NMIBC对BCG治疗反应中的预后作用。
方法
回顾性分析2017年至2022年间接受膀胱内BCG治疗的Ta和T1期无固有肌层浸润的癌症患者数据。对经尿道切除标本进行PD-L1、PD-L2和STAT3的免疫组化染色。
结果
59例患者的平均年龄为66.5 ±7.7岁，83.9%为男性。对BCG治疗完全缓解的患者比例为66.1%，BCG难治性患者比例为33.9%。人口学和临床数据根据BCG治疗反应无显著差异（P> 0.05）。TIL（肿瘤浸润淋巴细胞）（TILs）≥20%的患者比例在Ta期肿瘤中为9.7%，在T1期肿瘤中为46.4%（P = 0.0014）。肿瘤细胞评分（TCS）、免疫细胞评分（ICS）、联合评分（CS）以及PD-L1、PD-L2的表达水平和STAT3的H-score根据肿瘤分期和治疗反应无显著差异（P > 0.05）。然而，T1期患者中PD-L1的中位ICS和CS以及STAT3的中位H-score显著高于Ta期患者（P = 0.0487、0.0462、0.0112）。在BCG难治性患者中，T1期患者的中位STAT3显著高于Ta期患者（P = 0.0356），且T1期患者中TILs≥20%的仅3例（P = 0.031）。在所有患者中，PD-L1的TCS与STAT3的H-score之间（P = 0.0302）、PD-L1的ICS与PD-L2的TCS之间（P = 0.0053）以及TILs比例之间（P < 0.0001）均存在显著正相关。在BCG难治性病例中，治疗前和治疗后PD-L2的TCS与STAT3的H-score显著相关（P = 0.0361和0.0021）。
展开英文摘要原文
METHODS
The data of patients at the Ta and T1 stages of the cancer without muscularis propria invasion, who were treated with intravesical BCG therapy between 2017 and 2022 were retrospectively analyzed. Immunohistochemical staining for PD-L1, PD-L2, and STAT3 was performed on transurethral resection materials.
RESULTS
The mean age of 59 patients was 66.5 ±7.7 and 83.9% were male. The percentage of patients with complete response to BCG treatment was 66.1% and that of BCG refractory patients was 33.9%. Demographic and clinical data did not differ significantly according to BCG treatment response (P> 0.05). The proportion of patients with tumor-infiltrating lymphocytes (TILs) ≥20% were 9.7% among those with Ta-stage tumors and 46.4% among those with T1-stage tumors (P = 0.0014). The percentages of tumor cell scoring (TCS), immune cell scoring (ICS), combined scoring (CS), and expression levels of PD-L1, PD-L2, and H-score of STAT3 did not differ significantly according to tumor stage and treatment response (P > 0.05). However, the median ICS and CS for PD-L1 and median H-score for STAT3 were significantly higher among patients in T1 stage compared to those in Ta stage (P = 0.0487, 0.0462, 0.0112, respectively). Among BCG refractory patients, median STAT3 of patients in T1 stage was significantly higher than those at stage Ta (P = 0.0356) and the rate of TILs was ≥20% in only 3 patients in T1 stage (P = 0.031). Among all patients, significant positive correlation was found between TCS for PD-L1 and H-score for STAT3 (P = 0.0302); and between ICS for PD-L1 and TCS for PD-L2 (P = 0.0053) and TILs ratio (P < 0.0001). Among BCG-refractory cases, pretreatment and post-treatment TCS for PD-L2 and H-scores for STAT3 were significantly correlated (P = 0.0361 and 0.0021, respectively).
CONCLUSIONS
The success of BCG treatment in NMIBC was not related to PD-L1, PD-L2, and STAT3 expression status, but PD-L1 expression was correlated with both PD-L2 and STAT3 as well as TILs rate, but this correlation was lost after BCG treatment.
论文信息
- 作者
- Civriz AH、Teke K、Akdas EM、Dillioglugil O、Vural C、Yaprak Bayrak B
- 第一作者单位
- Department of Pathology, Faculty of Medicine, Kocaeli University, Kocaeli, Turkey.Turkey
- 通讯作者单位
- Department of Pathology, Faculty of Medicine, Kocaeli University, Kocaeli, Turkey. Electronic address: busra.yaprakbayrak@kocaeli.edu.tr.Turkey
- 期刊
- Urologic oncology2023 Dec
- 原文标识
- PubMed 37690934 · DOI 10.1016/j.urolonc.2023.08.012