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程序性细胞死亡蛋白在卡波西肉瘤和皮肤血管肉瘤中的表达。

Expression of Programmed Cell Death Proteins in Kaposi Sarcoma and Cutaneous Angiosarcoma.

机构信息

Department of Dermatology, Skin Cancer Center.

Institute for Prevention and Occupational Medicine of the German Social Accident Insurances, Ruhr-University Bochum (IPA), Bochum.

出版信息

J Immunother. 2020 Jun;43(5):169-174. doi: 10.1097/CJI.0000000000000317.

Abstract

Not only for cutaneous angiosarcoma (CAS) patients but also for advanced and therapy-refractory patients with classic Kaposi sarcoma (CKS) and human immunodeficiency virus (HIV)-associated Kaposi sarcoma (HIV-KS) there is a high need for more effective treatment modalities. The aim of this work was to study programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) protein expression and related immune parameters in CKS, HIV-KS, and CAS and correlate it with other immunologic parameters and clinical data. Immunohistochemistry was performed on formalin-fixed paraffin-embedded tumor tissue of 19 CKS, 7 HIV-KS, and 12 CAS patients using antibodies against the following (and they are): PD-1, PD-L1, CD4, CD8, CD56, and FOXP3. PD-1 expression significantly correlated with PD-L1 expression Moreover, PD-1 and PD-L1 expression significantly correlated with CD56 and FOXP3 expression. High intratumoral FOXP3 expression was significantly associated with disease relapse (P=0.029). CD4 and FOXP3 expression was significantly higher in CKS and CAS, as compared with HIV-KS. All in all, PD-1 and PD-L1 expression was relatively weak and did not significantly differ between CKS, HIV-KS, and CAS patients. Nevertheless, PD-1 was positive in 31.6% of CKS, 28.6% of HIV-KS, and 33.3% of CAS patients. PD-L1 was expressed in 36.6% of CKS, 28.6% of HIV-KS, and 41.7% of CAS patients. We have provided evidence that PD-1/PD-L1 signalling is of importance in angiosarcomas such as CKS, HIV-KS, and CAS. Our results support the notion that the use of PD-1/PD-L1 inhibitors may represent an effective strategy against these tumors.

摘要

不仅对于皮肤血管肉瘤(CAS)患者,而且对于晚期和治疗耐药的经典卡波西肉瘤(CKS)和人类免疫缺陷病毒(HIV)相关卡波西肉瘤(HIV-KS)患者,都需要更有效的治疗方法。本研究的目的是研究 CKS、HIV-KS 和 CAS 中程序性细胞死亡蛋白 1(PD-1)和程序性细胞死亡配体 1(PD-L1)蛋白表达及相关免疫参数,并将其与其他免疫参数和临床数据相关联。使用针对以下(并列举)的抗体对 19 例 CKS、7 例 HIV-KS 和 12 例 CAS 患者的福尔马林固定石蜡包埋肿瘤组织进行免疫组织化学染色:PD-1、PD-L1、CD4、CD8、CD56 和 FOXP3。PD-1 表达与 PD-L1 表达显著相关;此外,PD-1 和 PD-L1 表达与 CD56 和 FOXP3 表达显著相关。肿瘤内 FOXP3 高表达与疾病复发显著相关(P=0.029)。与 HIV-KS 相比,CD4 和 FOXP3 表达在 CKS 和 CAS 中显著升高。总之,PD-1 和 PD-L1 的表达相对较弱,在 CKS、HIV-KS 和 CAS 患者之间无显著差异。然而,PD-1 在 31.6%的 CKS、28.6%的 HIV-KS 和 33.3%的 CAS 患者中呈阳性。PD-L1 在 36.6%的 CKS、28.6%的 HIV-KS 和 41.7%的 CAS 患者中表达。我们已经提供了证据表明,PD-1/PD-L1 信号通路在 CKS、HIV-KS 和 CAS 等血管肉瘤中具有重要意义。我们的研究结果支持使用 PD-1/PD-L1 抑制剂可能是对抗这些肿瘤的有效策略的观点。

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