Department of Dermatology, Skin Cancer Center.
Institute for Prevention and Occupational Medicine of the German Social Accident Insurances, Ruhr-University Bochum (IPA), Bochum.
J Immunother. 2020 Jun;43(5):169-174. doi: 10.1097/CJI.0000000000000317.
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.
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。