CD274 (PD-L1) Copy Number Changes (Gain) & Response to Immune Checkpoint Blockade Therapy in Carcinomas of the Urinary Tract.
CD274 (PD-L1) Copy Number Changes (Gain) & Response to Immune Checkpoint Blockade Therapy in Carcinomas of the Urinary Tract.
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DOI：
10.3233/blc-201532
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Al-Ahmadie HA
中科院分区：
文献类型：
--
作者：
Gupta S;Vanderbilt CM;Zhang Y;Tickoo SK;Fine SW;Gopalan A;Chen YB;Sirintrapun SJ;Teo MY;Funt SA;Iyer G;Rosenberg JE;Bajorin DF;Bochner BH;Pietzak EJ;Ross DS;Ladanyi M;Cheville JC;Solit DB;Reuter VE;Al-Ahmadie HA
免疫检查点抑制剂是尿路上皮癌的重要治疗选择，但在少数患者中实现了持久的反应。鉴别治疗前的生物标记物是至关重要的，这些生物标记物可以预测对这些治疗的反应或表现出内在耐药性。探讨尿路上皮癌中PD-L1拷贝数改变的普遍性及其与免疫检查点抑制剂应答的相关性。我们对1050例膀胱癌和上尿路癌进行了前瞻性的靶向下一代测序。我们评估了PD-L1蛋白表达、拷贝数状态（下一代测序/FISH）和详细的治疗反应。我们鉴定了9例PD-L1扩增的肿瘤和9例PD-L1缺失的肿瘤。PD-L1蛋白在PD-L1扩增的肿瘤中表达最高。在9例肿瘤携带PD-L1扩增的患者中，6例接受了免疫治疗，其中4例获得临床获益，2例获得持久应答。在肿瘤PD-L1拷贝数丢失的9例患者中，4例接受了免疫治疗，3例出现疾病进展。如果在更大的队列中得到验证，PD-L1拷贝数改变可能作为尿路上皮癌患者免疫治疗反应的潜在生物标志物。
Immune checkpoint inhibitors are an important therapeutic option for urothelial carcinoma, but durable responses are achieved in a minority of patients. Identifying pre-treatment biomarkers that may predict response to these therapies or who exhibit intrinsic resistance, is of paramount importance. To explore the prevalence of PD-L1 copy number alteration in urothelial carcinoma and correlate with response to immune checkpoint inhibitors. We analyzed a cohort of 1050 carcinomas of the bladder and upper urinary tract that underwent targeted next generation sequencing, prospectively. We assessed PD-L1 protein expression, copy number status (next generation sequencing/FISH), and detailed treatment response. We identified 9 tumors with PD-L1 amplification and 9 tumors with PD-L1 deletion. PD-L1 protein expression was the highest in PD-L1 amplified tumors. Of the 9 patients whose tumors harbored PD-L1 amplification, 6 received immunotherapy with 4 deriving clinical benefit, and two achieving durable response. Of the 9 patients whose tumors had PD-L1 copy number losses, 4 received immunotherapy with 3 experiencing disease progression. PD-L1 copy number alterations may serve as potential biomarkers of response to immunotherapy in urothelial carcinoma patients, if validated in larger cohorts.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
8.8
作者：
Guo, Charles C.;Majewski, Tadeusz;Czerniak, Bogdan
通讯作者：
Czerniak, Bogdan
影响因子：
8.4
作者：
Zandberg, Dan P.;Algazi, Alain P.;Mesia, Ricard
通讯作者：
Mesia, Ricard
尿路上皮膀胱癌中非T细胞增长的肿瘤微环境的分子驱动因素。
影响因子：
10.1
作者：
Sweis RF;Spranger S;Bao R;Paner GP;Stadler WM;Steinberg G;Gajewski TF
通讯作者：
Gajewski TF
影响因子：
15.8
作者：
Snyder A;Nathanson T;Funt SA;Ahuja A;Buros Novik J;Hellmann MD;Chang E;Aksoy BA;Al-Ahmadie H;Yusko E;Vignali M;Benzeno S;Boyd M;Moran M;Iyer G;Robins HS;Mardis ER;Merghoub T;Hammerbacher J;Rosenberg JE;Bajorin DF
通讯作者：
Bajorin DF