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
非尿路上皮膀胱癌中共抑制性受体的表达谱：下一代免疫检查点抑制剂的临床前证据
英文原题：Expression Profiles of Co-Inhibitory Receptors in Non-Urothelial Bladder Cancer: Preclinical Evidence for the Next Generation of Immune Checkpoint Inhibitors.
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Expression Profiles of Co-Inhibitory Receptors in Non-Urothelial Bladder Cancer: Preclinical Evidence for the Next Generation of Immune Checkpoint Inhibitors.
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中文摘要
免疫检查点抑制是膀胱癌治疗的基石，但其在非尿路上皮亚型膀胱癌中的疗效有限，且预后仍然较差。因此，我们研究了免疫检查点分子 TIM-3、TIGIT 和 LAG-3 在膀胱鳞状细胞癌（SCC）和腺癌（ADENO）中的潜力。TIL（肿瘤浸润淋巴细胞）（TILs）在 SCC 和 ADENO 中均显示 TIM-3 和 TIGIT 高表达，而 LAG-3 阳性 TILs 在 ADENO 中缺失，在 46% 的 SCC 中存在。定量分析显示 TIM-3 在 SCC（r = -0.001，p = 0.997）和 ADENO（r = 0.135，p = 0.549）中的表达与年龄无关，而年龄增长与 SCC 队列中 TIGIT（r = 0.157，p = 0.242）和 LAG-3（0.106，p = 0.436）表达升高以及 ADENO 队列中 TIGIT（r = 0.276，p = 0.214）表达升高相关。男性患者在 ADENO 中显示 TIGIT 评分升高（p < 0.01）。
值得注意的是，TIM-3-TILs 高浸润（p = 0.048）与 SCC 中更差的无进展生存期相关。这些结果突出了共抑制受体在非尿路上皮膀胱癌亚型中的差异表达，并为新的治疗靶点提供了临床前证据。在临床试验前进行生物标志物检测对于识别最适合靶向免疫治疗的患者至关重要。
展开英文摘要原文
Immune checkpoint inhibition is a cornerstone of bladder cancer therapy, but its efficacy in non-urothelial subtypes of bladder cancer is limited, and the prognosis remains poor.
Therefore, we investigated the potential of the immune checkpoint molecules TIM-3, TIGIT, and LAG-3 in squamous-cell carcinoma (SCC) and adenocarcinoma (ADENO) of the urinary bladder. Tumor-infiltrating lymphocytes (TILs) showed a high expression of TIM-3 and TIGIT in both SCC and ADENO, while LAG-3-positive TILs were absent in ADENO and present in 46% of SCC. Quantitative analysis revealed age-independent expression of TIM-3 in SCC (r = -0. 001, p = 0. 997) and ADENO (r = 0. 135, p = 0. 549), with increasing age correlating with higher expression of TIGIT (r = 0. 157, p = 0. 242) and LAG-3 (0.
106, p = 0. 436) in the SCC cohort and of TIGIT (r = 0. 276, p = 0. 214) in the ADENO cohort. Male patients showed increased TIGIT scores in ADENO ( p < 0. 01). Of note, a high infiltration of TIM-3-TILs ( p = 0. 048) correlated with worse progression-free survival in SCC.
These results highlight the differential expression of co-inhibitory receptors in non-urothelial bladder cancer subtypes and provide preclinical evidence for new therapeutic targets. Biomarker testing prior to clinical trials is essential for identifying the most suitable patients for targeted immunotherapy.
论文信息
- 作者
- Rodler S、Ledderose ST、Waidelich R、Kohler J、Sendelhofert A、Casuscelli J、Schulz G、Stief CG
- 单位
- Department of Urology, University Hospital of Ludwig-Maximilian-University, 81377 Munich, Germany.Germany
- 期刊
- Cancers2025 Jul 1
- 原文标识
- PubMed 40647508 · DOI 10.3390/cancers17132210
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