Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Cancer Med. 2022 Jan;11(2):479-491. doi: 10.1002/cam4.4444. Epub 2021 Dec 14.
Programmed cell death ligand 1 (PD-L1) status has been reported to be different between metastatic and primary lesions in some cases. Therefore, the interaction between carcinoma and immune cells could influence their expression in the tumor microenvironment. PD-L1 is known to bind not only to Programmed cell death 1 (PD-1) but also to B7-1 (CD80). In this study, we examined the interaction between lung carcinoma cell lines and peripheral blood mononuclear cells (PBMCs) in vitro. We then examined the significance of B7-1 expression non-small cell lung cancer (NSCLC) microenvironment.
The interaction of lung carcinoma cell lines and PBMC through the soluble factors was analyzed using a co-culture system. The changes in expression of immune checkpoint-related factors in PBMC were examined by PD-1/PD-L1 Checkpoint Pathway qPCR Array Kit. B7-1 expression in NSCLC tissues was examined by immunohistochemistry.
B7-1 was upregulated following the co-culture with the lung carcinoma cell lines. B7-1 expression in NSCLC tissues was significantly higher in smokers and squamous cell carcinomas and was significantly positively correlated with PD-L1 status in primary cancer. However, B7-1 and PD-1 were not correlated between primary and metastatic diseases in the same patients.
PD-1 inhibitors inhibited PD-1/PD-L1 binding but not PD-L1/B7-1 binding. These results demonstrated that the intratumoral ratio of B7-1 positive T cells in NSCLC tissue could be involved in the therapeutic efficacy of PD-L1 inhibitors. This study focused on lymph node metastasis but other sites of distant metastases should be explored by further analysis.
在某些情况下，转移性和原发性病变中的程序性细胞死亡配体 1（PD-L1）状态有所不同。因此，癌细胞与免疫细胞之间的相互作用可能会影响它们在肿瘤微环境中的表达。PD-L1 不仅与程序性细胞死亡 1（PD-1）结合，还与 B7-1（CD80）结合。在这项研究中，我们在体外研究了肺癌细胞系与外周血单核细胞（PBMC）之间的相互作用。然后，我们研究了非小细胞肺癌（NSCLC）微环境中 B7-1 表达的意义。
通过共培养系统分析肺癌细胞系与 PBMC 之间通过可溶性因子的相互作用。通过 PD-1/PD-L1 检查点途径 qPCR 试剂盒检查 PBMC 中免疫检查点相关因子表达的变化。通过免疫组织化学检查 NSCLC 组织中的 B7-1 表达。
与肺癌细胞系共培养后，B7-1 上调。吸烟者和鳞状细胞癌的 NSCLC 组织中 B7-1 表达明显升高，与原发性癌症中的 PD-L1 状态呈显著正相关。然而，同一患者的原发性和转移性疾病之间的 B7-1 和 PD-1 之间没有相关性。
PD-1 抑制剂抑制了 PD-1/PD-L1 结合，但不抑制 PD-L1/B7-1 结合。这些结果表明，NSCLC 组织中 B7-1 阳性 T 细胞的肿瘤内比值可能参与了 PD-L1 抑制剂的治疗效果。本研究重点关注淋巴结转移，但应通过进一步分析探索其他远处转移部位。
