Department of Thoracic Surgery, Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan.
Department of Clinical Immunology and Rheumatology, Tazuke Kofukai Medical Research Institute, Kitano Hospital, Osaka, Japan.
Lung Cancer. 2019 Oct;136:136-144. doi: 10.1016/j.lungcan.2019.08.023. Epub 2019 Aug 31.
PD-L1 expression on tumor cells (TCs) and tumor-infiltrating immune cells (ICs) plays important roles in regulating the antitumor T cell response. However, the mechanistic and clinical significance of the effect of PD-L1 on TCs versus ICs remains unclear. On the other hand, tumor-associated macrophages (TAMs), M2 macrophages in particular, can promote tumor progression.
We evaluated PD-L1 expression on TCs and ICs using Ventana SP263 assay and the stromal M2 TAM distribution using CD163 staining in 160 consecutive patients with resected non-small cell lung cancer (NSCLC).
PD-L1 expression on TCs and ICs was significantly higher in stromal M2 TAM-high group than in stromal M2 TAM-low group (p < 0.001 and p < 0.001, respectively). Regarding the clinical significance of PD-L1, PD-L1 expression on TCs was significantly associated with histology (p = 0.001), tumor differentiation (p < 0.001) and nodal status (p = 0.029). Furthermore, PD-L1 expression on ICs was significantly associated with histology (p < 0.001), tumor differentiation (p < 0.001), tumor status (p = 0.024), nodal status (p = 0.016), and pathologic stage (p = 0.004). The disease-free survival rate was significantly lower in patients with PD-L1-positive TC than in those with PD-L1-negative TC (p = 0.023), as well as in patients with PD-L1-positive IC than in those with PD-L1-negative IC (p < 0.001). Furthermore, the overall survival rate was significantly lower in patients with PD-L1-positive IC than in those with PD-L1-negative IC (p = 0.023).
During tumor progression in NSCLC, the presence of M2 TAMs might affect PD-L1 expression both on TCs and ICs. In patients with NSCLC, PD-L1 expression both on TCs and ICs was associated with malignant behaviors, which was more in case of ICs.
肿瘤细胞（TCs）和肿瘤浸润免疫细胞（ICs）上的 PD-L1 表达在调节抗肿瘤 T 细胞反应中起着重要作用。然而，PD-L1 对 TCs 和 ICs 的影响的机制和临床意义尚不清楚。另一方面，肿瘤相关巨噬细胞（TAMs），尤其是 M2 巨噬细胞，可以促进肿瘤进展。
我们使用 Ventana SP263 检测法评估了 160 例连续接受手术切除的非小细胞肺癌（NSCLC）患者的 TCs 和 ICs 上的 PD-L1 表达，并使用 CD163 染色评估了基质中 M2 TAM 的分布。
基质中 M2 TAM 高组的 TCs 和 ICs 上的 PD-L1 表达明显高于基质中 M2 TAM 低组（分别为 p<0.001 和 p<0.001）。关于 PD-L1 的临床意义，TCs 上的 PD-L1 表达与组织学（p=0.001）、肿瘤分化（p<0.001）和淋巴结状态（p=0.029）显著相关。此外，ICs 上的 PD-L1 表达与组织学（p<0.001）、肿瘤分化（p<0.001）、肿瘤状态（p=0.024）、淋巴结状态（p=0.016）和病理分期（p=0.004）显著相关。PD-L1 阳性 TC 患者的无病生存率明显低于 PD-L1 阴性 TC 患者（p=0.023），PD-L1 阳性 IC 患者的无病生存率明显低于 PD-L1 阴性 IC 患者（p<0.001）。此外，PD-L1 阳性 IC 患者的总生存率明显低于 PD-L1 阴性 IC 患者（p=0.023）。
在 NSCLC 肿瘤进展过程中，M2 TAMs 的存在可能会影响 TCs 和 ICs 上的 PD-L1 表达。在 NSCLC 患者中，TCs 和 ICs 上的 PD-L1 表达与恶性行为相关，而 ICs 上的相关性更强。
