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Abstract：
Programmed cell death 1 ligand 1), programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), T-cell immunoglobulin and mucin-domain containing-3, lymphocyte activation gene-3, and T-cell immunoglobulin and ITIM domain (TIGIT) are considered major immune co-inhibitory receptors (CIRs) and the most promising immunotherapeutic targets in cancer treatment, but they are largely unexplored in upper tract urothelial carcinoma (UTUC). The aim of this Cohort Study was to provide evidence concerning expression profiles and the clinical significance of CIRs among Chinese UTUC patients. A total of 175 UTUC patients who received radical surgery in our center were included. We used immunohistochemistry to evaluate CIR expressions in tissue microarrays (TMAs). Clinicopathological characteristics and prognostic correlations of CIR proteins were retrospectively analyzed. TIGIT, T-cell immunoglobulin and mucin-domain containing-3, PD-1, CTLA-4, Programmed cell death 1 ligand 1, and lymphocyte activation gene-3 high expression was examined in 136(77.7%), 86(49.1%), 57(32.6%), 18(10.3%), 28(16.0%), and 18(10.3%) patients, respectively. Log-rank tests and Multivariate Cox analysis both implied CTLA-4 and TIGIT expression was associated with worse relapse-free survival. In conclusion, this is the largest Chinese UTUC cohort study, and we analyzed the Co-inhibitory receptor expression profiles in UTUC. We identified CTLA-4 and TIGIT expression as promising biomarkers for tumor recurrence. Furthermore, a subset of advanced UTUCs are probably immunogenic, for which single or combined immunotherapy may be potential therapeutic approaches in the future.
摘要：
程序性细胞死亡1配体1)，程序性细胞死亡蛋白-1（PD-1），细胞毒性T淋巴细胞抗原4（CTLA-4），T细胞免疫球蛋白和含粘蛋白结构域-3，淋巴细胞活化基因-3，T细胞免疫球蛋白和ITIM结构域（TIGIT）被认为是主要的免疫共抑制受体（CIR）和癌症治疗中最有希望的免疫治疗靶标。但它们在上尿路尿路上皮癌（UTUC）中尚未被研究。这项队列研究的目的是提供有关中国UTUC患者中CIRs表达谱和临床意义的证据。共有175例UTUC患者在我们中心接受根治性手术。我们使用免疫组织化学评估组织微阵列（TMAs）中CIR的表达。回顾性分析CIR蛋白的临床病理特征和预后相关性。TIGIT,在136（77.7％）中检测到T细胞免疫球蛋白和粘蛋白结构域包含-3，PD-1，CTLA-4，程序性细胞死亡1配体1和淋巴细胞活化基因3的高表达，86（49.1%），57（32.6%），18（10.3%），28（16.0%），和18名(10.3%)患者，分别。Log-rank检验和多变量Cox分析均提示CTLA-4和TIGIT表达与更差的无复发生存率相关。总之,这是中国最大的UTUC队列研究，我们分析了UTUC中的共抑制受体表达谱。我们确定CTLA-4和TIGIT表达是肿瘤复发的有希望的生物标志物。此外，一部分晚期UTUC可能具有免疫原性，单一或联合免疫治疗可能是未来潜在的治疗方法。
