Infiltration of CD8 T Cells and Expression of PD-1 and PD-L1 in Synovial Sarcoma.
Infiltration of CD8 T Cells and Expression of PD-1 and PD-L1 in Synovial Sarcoma.
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DOI：
10.1158/2326-6066.cir-16-0148
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发表时间：
2017-02
影响因子：
10.1
通讯作者：
Ribas A
中科院分区：
文献类型：
--
作者：
Nowicki TS;Akiyama R;Huang RR;Shintaku IP;Wang X;Tumeh PC;Singh A;Chmielowski B;Denny C;Federman N;Ribas A
表达程序性死亡配体1（PD-L1）的肿瘤与CD 8 T细胞表面上产生相应负信号的免疫受体PD-1相互作用，从而抑制抗肿瘤活性。阻断这种相互作用的治疗剂通过恢复功能性抗肿瘤T细胞活性在各种癌症中显示出希望。我们对29例临床滑膜肉瘤样本进行了回顾性分析，探讨了PD-L1、PD-1和CD 8表达的程度。使用定量免疫组织化学和多重免疫荧光来确定肿瘤内区域和肿瘤与周围非肿瘤组织之间的界面（即，侵袭边缘），以及这些因素的共定位。转移性肿瘤浸润边缘PD-L1、PD-1和CD 8细胞密度均显著高于原发性肿瘤（P < 0.01），且PD-L1、PD-1和CD 8细胞密度均呈正相关（P < 0.0001）。肿瘤浸润边缘的PD-1细胞密度与无进展生存率显著相关。多重免疫荧光证实了PD-1和CD 8在浸润边缘内的淋巴细胞上的共表达，以及PD-1+ CD 8细胞和PD-L1+肿瘤细胞之间的相对接近。我们的研究结果为筛选滑膜肉瘤患者的CD 8，PD-1和PD-L1共定位提供了临床前依据，这可能是PD-1阻断治疗反应的标志物。
Tumors expressing programmed death ligand 1 (PD-L1) interact with the corresponding negative-signal generating immune receptor on the surface of CD8 T cells, PD-1, thereby suppressing antitumor activity. Therapeutics blocking this interaction have shown promise in various cancers by restoring functional antitumor T-cell activity. We explored the degree of PD-L1, PD-1, and CD8 expression in a retrospective analysis of 29 clinical synovial sarcoma samples. Quantitative immunohistochemistry and multiplex immunofluorescence were used to determine relative quantification of CD8+ and PD-1+ T cells and PD-L1 expression within the intratumor area and the interface between the tumor and the surrounding nontumor tissue (i.e., invasive margin), and colocalization of these factors, respectively. PD-L1, PD-1, and CD8 cell densities in the tumor invasive margins were significantly higher in the metastatic tumors than the primary tumors (P < 0.01), and PD-L1, PD-1, and CD8 cell densities were all significantly positively correlated with one other (P < 0.0001). PD-1 cell density in the tumor invasive margin was significantly associated with worse progression-free survival. Multiplex immunofluorescence demonstrated co-expression of PD-1 and CD8 on lymphocytes within the invasive margin, as well as relative proximity between PD-1+ CD8 cells and PD-L1+ tumor cells. Our results provide a preclinical rationale for screening of patients with synovial sarcoma for the colocalization of CD8, PD-1, and PD-L1, which may be a marker for response to PD-1 blockade therapy.