Department of Radiation Oncology, Unicancer-Georges-Francois Leclerc Cancer Center, 21079 Dijon, France.
Immunomolecular Therapies in Cancer (TIMC), INSERM UMR1098, 25000 Besancon, France.
Cells. 2020 Sep 10;9(9):2071. doi: 10.3390/cells9092071.
In locally advanced rectal cancer, radiotherapy (RT) followed by surgery have improved locoregional control, but distant recurrences remain frequent. Although checkpoint inhibitors have demonstrated objective response in several cancers, the clinical benefit of PD-1/PD-L1 blockade remains uncertain in rectal cancer. We collected data from biopsies and surgical specimens in 74 patients. The main objective was to evaluate the impact of neoadjuvant RT and fractionation on PD-L1 expression. Secondary objectives were to study the relation between PD-L1 expression and tumor regression grade (TRG), progression-free survival (PFS), overall survival (OS), and CD8 TILs infiltration. Median rates of cells expressing PD-L1 pre- and post-RT were 0.15 (range, 0-17) and 0.5 (range, 0-27.5), respectively ( = 0.0005). There was no effect of RT fractionation on PD-L1+ cell rates. We found no relation between CD8+ TILs infiltration and PD-L1 expression and no difference between high-PD-L1 or low-PD-L1 expression and TRG. High-to-high PD-L1 expression profile had none significant higher OS and PFS compared to all other groups ( = 0.06). Median OS and PFS were higher in biopsies with >0.08 PD-L1+ cells. High-to-high PD-L1 profile and ypT0-2 were significantly associated with higher OS and PFS. This study did not show the differential induction of PD-L1 expression according to fractionation.
在局部晚期直肠癌中,放疗(RT)联合手术可提高局部区域控制率,但远处复发仍很常见。尽管检查点抑制剂在几种癌症中显示出了客观的反应,但 PD-1/PD-L1 阻断在直肠癌中的临床获益仍不确定。我们从 74 名患者的活检和手术标本中收集了数据。主要目的是评估新辅助 RT 及分割对 PD-L1 表达的影响。次要目的是研究 PD-L1 表达与肿瘤退缩分级(TRG)、无进展生存期(PFS)、总生存期(OS)和 CD8 TILs 浸润之间的关系。RT 前后 PD-L1 表达的细胞中位数分别为 0.15(范围,0-17)和 0.5(范围,0-27.5)( = 0.0005)。RT 分割对 PD-L1+细胞率没有影响。我们没有发现 CD8+TILs 浸润与 PD-L1 表达之间的关系,也没有发现高 PD-L1 或低 PD-L1 表达与 TRG 之间的差异。高 PD-L1 表达与高 PD-L1 表达的患者 OS 和 PFS 无显著差异( = 0.06)。活检中 PD-L1+细胞>0.08 的患者 OS 和 PFS 较高。高 PD-L1 表达和 ypT0-2 与 OS 和 PFS 较高显著相关。本研究没有显示根据分割诱导 PD-L1 表达的差异。