Mletzko Salvinia, Pinato David J, Robey Rebecca C, Dalla Pria Alessia, Benson Peter, Imami Nesrina, Bower Mark
Imperial College London, London, UK.
Chelsea and Westminster Hospital, London, UK.
Oncoimmunology. 2017 Apr 7;6(8):e1304337. doi: 10.1080/2162402X.2017.1304337. eCollection 2017.
Upregulation of programmed death ligand 1 (PD-L1) is a mechanism of immune escape utilized by a variety of tumors. PD-L1 expression in tumor cells or in the surrounding infiltrate correlates with clinical responsiveness to novel therapies targeting the PD-1/PD-L1 immune checkpoint. In the context of HIV-1 infection, Kaposi's sarcoma (KS) is largely responsive to restoration of immunity following combination antiretroviral therapy (cART), but there is a subset that is not. We hypothesized that this subset of cART-refractory KS may utilize the PD-L1 pathway of immune escape. We found that PD-L1 expressing KS had a denser CD8 T cell ( = 0.03) and PD-L1 positive macrophage peritumoral infiltrate ( = 0.04) to suggest the involvement of PD-L1 in shaping an immune-tolerogenic microenvironment in cART-refractory KS. The presence of PD-L1 expression in association with immune-infiltrating cells provides rationale for the clinical development PD-1/PD-L1-targeted checkpoint inhibitors in cART-refractory KS.
程序性死亡配体1(PD-L1)的上调是多种肿瘤利用的一种免疫逃逸机制。肿瘤细胞或周围浸润细胞中的PD-L1表达与针对PD-1/PD-L1免疫检查点的新型疗法的临床反应性相关。在HIV-1感染的背景下,卡波西肉瘤(KS)在接受联合抗逆转录病毒治疗(cART)后,很大程度上对免疫恢复有反应,但有一部分患者并非如此。我们假设,这部分对cART难治的KS可能利用了PD-L1免疫逃逸途径。我们发现,表达PD-L1的KS有更密集的CD8 T细胞(P = 0.03)和肿瘤周围浸润的PD-L1阳性巨噬细胞(P = 0.04),这表明PD-L1参与了在对cART难治的KS中塑造免疫耐受微环境。PD-L1表达与免疫浸润细胞的存在为在对cART难治的KS中临床开发靶向PD-1/PD-L1的检查点抑制剂提供了理论依据。