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程序性死亡配体1(PD-L1)表达与宫颈癌肿瘤浸润淋巴细胞及新辅助化疗反应相关。

PD-L1 Expression Correlates With Tumor Infiltrating Lymphocytes And Response To Neoadjuvant Chemotherapy In Cervical Cancer.

作者信息

Meng Ying, Liang Huyi, Hu Jianguo, Liu Shuaibin, Hao Xiaoming, Wong Micheal Sze Ka, Li Xiaoyi, Hu Lina

机构信息

Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China.

Lee's Pharmaceutical (Hong Kong) Limited, Hong Kong 999077, P.R. China.

出版信息

J Cancer. 2018 Jul 30;9(16):2938-2945. doi: 10.7150/jca.22532. eCollection 2018.

Abstract

Programmed death-ligand 1 (PD-L1) has been reported to be expressed in many types of tumor cells, and bind to PD-1 on T lymphocytes to inhibit immune response. Immunologic checkpoint blockade with antibodies that target the PD1/PD-L1 pathway has demonstrated to have impressive antitumor effects on many malignancies. However, the significance of PD1/PD-L1 pathway in cervical cancer remains unclear. Here we studied PD-L1, PD-1, CD8 and HPV expression in cervical cancer and normal cervix by immunohistochemical staining. Our results showed that there was more frequently positive for PD-L1, PD-1 and CD8 in cervical cancer tissues compared to normal tissues, especially those strongly stained HPV. Additionally, PD-L1, PD-1 and CD8 were more frequently stained in tissues from advanced tumor and tumor with lymphoid nodes or vascular invasion respectively. Tissues from patients with chemotherapy history had over expression of PD-L1 in tumor cells and more PD-1 and CD8 in stromal mononuclear cells, which were identified as tumor infiltrated lymphocytes (TILs). These findings point to a key role of PD-L1 in immune escape of cervical cancer, and provide a rationale for therapeutic targeting of the PD-1/PD-L1 pathway.

摘要

据报道,程序性死亡配体1(PD-L1)在多种肿瘤细胞中表达,并与T淋巴细胞上的PD-1结合以抑制免疫反应。用靶向PD1/PD-L1通路的抗体进行免疫检查点阻断已证明对许多恶性肿瘤具有显著的抗肿瘤作用。然而,PD1/PD-L1通路在宫颈癌中的意义仍不清楚。在此,我们通过免疫组织化学染色研究了宫颈癌和正常宫颈组织中PD-L1、PD-1、CD8和HPV的表达。我们的结果显示,与正常组织相比,宫颈癌组织中PD-L1、PD-1和CD8呈阳性的频率更高,尤其是那些HPV强染色的组织。此外,PD-L1、PD-1和CD8在晚期肿瘤组织以及分别伴有淋巴结转移或血管浸润的肿瘤组织中染色更频繁。有化疗史患者的组织中,肿瘤细胞中PD-L1过表达,基质单核细胞中PD-1和CD8更多,这些细胞被鉴定为肿瘤浸润淋巴细胞(TILs)。这些发现表明PD-L1在宫颈癌免疫逃逸中起关键作用,并为靶向PD-1/PD-L1通路的治疗提供了理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc3f/6096364/019ef6a4db97/jcav09p2938g001.jpg

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