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
雄激素受体、ADAR2 和 PD-L1 在卡介苗治疗的原发性膀胱尿路上皮原位癌中的作用
英文原题：Roles for Androgen Receptor, ADAR2, and PD-L1 in Primary Urothelial Carcinoma In Situ of the Bladder Treated with Bacillus Calmette-Guérin Therapy.
查看英文原题
Roles for Androgen Receptor, ADAR2, and PD-L1 in Primary Urothelial Carcinoma In Situ of the Bladder Treated with Bacillus Calmette-Guérin Therapy.
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中文摘要
在这项回顾性观察性多中心研究中，我们确定了彼此相关的肿瘤和免疫标志物，这可能有助于选择对卡介苗（BCG）治疗反应更好的膀胱原发性尿路上皮原位癌（CIS）患者。研究了73例接受BCG同质治疗的膀胱原发性CIS患者。通过免疫组织化学分析以CD4/CD8比值衡量的TIL（肿瘤浸润淋巴细胞）（TILs）、雄激素受体（AR）、作用于RNA的腺苷脱氨酶1（ADAR1）、作用于RNA的腺苷脱氨酶2（ADAR2）和程序性死亡配体1（PD-L1）的表达，而miR-200a-3p和INF-γ则与临床病理特征和无复发生存期相关。CIS中高AR水平与较高的ADAR1表达、较低的ADAR2表达、较高的PD-L1 TPS、较高的CD4/CD8比值以及CIS的多灶性显著相关（P < .001）。具有上述特征的所有患者无复发生存期均显著较差（P < .0001）。多因素和多变量回归分析证实了AR、ADAR2和PD-L1的预测作用，尤其是当这3个参数联合时。
此外，我们证明AR较低和ADAR2表达较高的患者miR-200a-3p和INF-γ水平显著高于AR较高和ADAR2表达较低的患者（分别为P = .0011和P = .0002）。
我们的发现突出了AR通过ADAR2、miR-200a-3p和INF-γ通路调节PD-L1表达和TILs，从而在BCG治疗反应中的作用。
此外，我们的数据为优化CIS患者的BCG治疗提供了有价值的见解，为其他可能的联合治疗策略铺平了道路。
展开英文摘要原文
In this retrospective observational multicenter study, we identified tumors and immune markers that are related to each other, which could help in selecting patients with bladder primary urothelial carcinoma in situ (CIS) who responded better to Bacillus Calmette-Guérin (BCG) therapy. Seventy-three patients with primary bladder CIS who were homogeneously treated with BCG were studied. Tumor-infiltrating lymphocytes (TILs) measured as CD4/CD8 ratio, androgen receptor (AR), adenosine deaminase acting on RNA 1 (ADAR1), adenosine deaminase acting on RNA 2 (ADAR2), and programmed death ligand 1 (PD-L1) expression were analyzed using immunohistochemistry, whereas miR-200a-3p and INF-γ were correlated with clinicopathological features and recurrence-free survival.
High AR levels in CIS were significantly associated with higher ADAR1 expression, lower ADAR2 expression, higher PD-L1 TPS, higher CD4/CD8 ratio, and multifocality of CIS (P < . 001). All patients with the above-mentioned characteristics had significantly worse recurrence-free survival (P < . 0001). Multivariate and multiple regression analyses confirmed the predictive role of AR, ADAR2, and PD-L1, especially when all 3 parameters were combined.
Additionally, we demonstrated that patients with lower AR and higher ADAR2 expressions had significantly higher levels of miR-200a-3p and INF-γ than those with higher AR and lower ADAR2 expression (P = . 0011 and P = . 0002, respectively).
Our findings highlight the role of AR in the response to BCG therapy by modulating PD-L1 expression and TILs through the ADAR2, miR-200a-3p, and INF-γ pathways.
Furthermore, our data provide valuable insights for optimizing BCG therapy in patients with CIS, paving the way for other possible combined treatment strategies.
论文信息
- 作者
- Ricciardi G、Fiorentino V、Pierconti F、Giordano WG、Germanà E、Ieni A、Palermo G、Racioppi M
- 第一作者单位
- Department of Biomedical, Dental, Morphological and Functional Imaging Sciences, University of Messina, Messina, Italy; Istituto Clinico Polispecialistico C.O.T. Cure Ortopediche Traumatologiche s.p.a., Messina, Italy.Italy
- 通讯作者单位
- Department of Human Pathology of Adults and Developmental Age "Gaetano Barresi", Division of Pathology, University of Messina, Messina, Italy. Electronic address: maurizio.martini@unime.it.Italy
- 文献类型
- 观察性研究 · 多中心研究
- 期刊
- Laboratory investigation; a journal of technical methods and pathology2025 May
- 原文标识
- PubMed 40010639 · DOI 10.1016/j.labinv.2025.104120