Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
Specialized Translational Services Laboratory, Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.
Clin Cancer Res. 2020 Oct 15;26(20):5456-5461. doi: 10.1158/1078-0432.CCR-20-1303. Epub 2020 Jul 24.
In both the IMpassion 130 trial in the metastatic setting and in Keynote 522 in the neoadjuvant setting, patients with triple-negative breast cancer (TNBC) showed benefit from PD-1 axis immunotherapy. Here, we assess PD-L1 expression on both tumor and immune cells using quantitative immunofluorescence to assess association with benefit from neoadjuvant durvalumab concurrent with chemotherapy in TNBC.
Pretreatment core needle biopsies ( = 69) were obtained from patients who participated in a phase I/II clinical trial (NCT02489448). The final analysis included 45 patients [pathologic complete response (pCR) = 18, non-pCR = 27] due to technical issues and insufficient tissue. Slides were stained using a previously validated Ultivue DNA-based Ultimapper kit (CD8, CD68, PD-L1, Cytokeratin/Sox10, and Hoechst counterstain). The PD-L1 expression was analyzed by molecular compartmentalization without segmentation using AQUA software (version 3.2.2.1) in three tissue compartments including tumor (cytokeratin-positive cells), CD68 cells, and overall stroma.
In patients with pCR, PD-L1 expression was significantly higher in tumor cells, in CD68 cells and in the stroma compared with patients non-pCR. There was no difference in the amount of CD68 cells in the tumor or stromal compartments between cases with pCR and non-pCR.
Expression of PD-L1 in tumor cells, immune cells in stroma, and colocalized with CD68 cells is associated with higher rates of pCR to durvalumab and chemotherapy in TNBC.
在转移性疾病的 IMpassion 130 试验和新辅助治疗的 Keynote 522 试验中，三阴性乳腺癌（TNBC）患者从 PD-1 轴免疫治疗中获益。在此，我们使用定量免疫荧光法评估肿瘤和免疫细胞上的 PD-L1 表达，以评估其与 TNBC 患者接受新辅助 durvalumab 联合化疗获益的相关性。
从参加 I/II 期临床试验的患者（NCT02489448）中获得预处理的核心针活检（=69）。由于技术问题和组织不足，最终分析包括 45 例患者[病理完全缓解（pCR）=18 例，非 pCR=27 例]。使用先前验证的 Ultivue DNA 基础 Ultimapper 试剂盒（CD8、CD68、PD-L1、细胞角蛋白/Sox10 和 Hoechst 复染）对切片进行染色。使用 AQUA 软件（版本 3.2.2.1）通过分子分区化而不进行分割对 PD-L1 表达进行分析，三个组织分区包括肿瘤（细胞角蛋白阳性细胞）、CD68 细胞和总体基质。
在 pCR 患者中，肿瘤细胞、CD68 细胞和基质中的 PD-L1 表达明显高于非 pCR 患者。pCR 与非 pCR 病例之间，肿瘤或基质区的 CD68 细胞数量没有差异。
肿瘤细胞、基质中免疫细胞以及与 CD68 细胞共定位的 PD-L1 表达与 TNBC 患者接受 durvalumab 和化疗后更高的 pCR 率相关。
