Department of Surgical Oncology, Hiroshima University, Hiroshima, Japan; Department of Anatomical Pathology, Hiroshima University, Hiroshima, Japan.
Department of Surgical Oncology, Hiroshima University, Hiroshima, Japan.
Clin Lung Cancer. 2020 Jul;21(4):e302-e314. doi: 10.1016/j.cllc.2020.01.013. Epub 2020 Jan 27.
The programmed death 1/programmed death-ligand 1 (PD-L1) pathway reportedly is as an important factor determining effects of immunotherapy; however, its prognostic impact is controversial, and its association with the surrounding immune microenvironment has not yet been elucidated.
We retrospectively analyzed 126 patients with pathologic stage I non-small-cell lung cancer. Patients with lepidic-dominant adenocarcinoma were excluded. PD-L1 expression was evaluated with immunohistochemistry correlated with clinicopathologic features and surrounding immune microenvironment status, including CD4, CD8, regulatory T cells, and human leukocyte antigen class I. Factors affecting prognosis were assessed by Kaplan-Meier and Cox regression analyses.
Twenty-three (18.3%) patients were positive for PD-L1 expression. No significant correlation was observed between PD-L1 expression and the surrounding immune microenvironment status. The PD-L1-positive group had a worse prognosis than the PD-L1-negative group (5-year recurrence-free survival rates, 63.4% vs. 81.0%; P = .061). Among surrounding immune cells, intratumoral CD8 status had the strongest impact on prognosis (P = .12). In the intratumoral CD8-high group, PD-L1 expression demonstrated no significant prognostic impact, whereas in the intratumoral CD8-low group, patients positive for PD-L1 demonstrated a significantly worse prognosis than those negative for PD-L1 (5-year recurrence-free survival rates, 41.7% vs. 78.6%; P = .034). Multivariable Cox regression analysis revealed that 'PD-L1-positive and intratumoral CD8-low' status was an independent prognostic factor (hazard ratio, 3.80; 95% confidence interval, 1.22-10.5; P = .023).
The prognostic impact of the PD-1/PD-L1 pathway may be distinct according to concurrent intratumoral CD8 status.
程序性死亡受体 1/程序性死亡配体 1（PD-L1）通路被认为是决定免疫治疗效果的一个重要因素；然而，其预后影响仍存在争议，且其与周围免疫微环境的关系尚未阐明。
我们回顾性分析了 126 例病理分期为 I 期非小细胞肺癌患者。排除以贴壁为主型腺癌为主的患者。采用免疫组织化学法检测 PD-L1 表达，并与临床病理特征及周围免疫微环境状态相关联，包括 CD4、CD8、调节性 T 细胞和人类白细胞抗原 I 类。采用 Kaplan-Meier 和 Cox 回归分析评估影响预后的因素。
23 例（18.3%）患者 PD-L1 表达阳性。PD-L1 表达与周围免疫微环境状态之间无显著相关性。PD-L1 阳性组的预后较 PD-L1 阴性组差（5 年无复发生存率，63.4%比 81.0%；P=0.061）。在周围免疫细胞中，肿瘤内 CD8 状态对预后的影响最强（P=0.12）。在肿瘤内 CD8 高组中，PD-L1 表达对预后无显著影响，而在肿瘤内 CD8 低组中，PD-L1 阳性患者的预后明显差于 PD-L1 阴性患者（5 年无复发生存率，41.7%比 78.6%；P=0.034）。多变量 Cox 回归分析显示，“PD-L1 阳性且肿瘤内 CD8 低”状态是独立的预后因素（危险比，3.80；95%置信区间，1.22-10.5；P=0.023）。
PD-1/PD-L1 通路的预后影响可能根据肿瘤内 CD8 状态的不同而不同。
