PD-L1 Protein Expression on Both Tumor Cells and Macrophages are Associated with Response to Neoadjuvant Durvalumab with Chemotherapy in Triple-negative Breast Cancer.
PD-L1 Protein Expression on Both Tumor Cells and Macrophages are Associated with Response to Neoadjuvant Durvalumab with Chemotherapy in Triple-negative Breast Cancer.
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DOI：
10.1158/1078-0432.ccr-20-1303
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发表时间：
2020-10-15
期刊：
影响因子：
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通讯作者：
Rimm DL
中科院分区：
文献类型：
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作者：
Ahmed FS;Gaule P;McGuire J;Patel K;Blenman K;Pusztai L;Rimm DL
在转移性背景下的IMpassion 130试验和新辅助治疗背景下的Keynote 522试验中，三阴性乳腺癌（TNBC）患者显示出从PD-1轴免疫治疗中获益。在这里，我们使用定量免疫荧光评估肿瘤和免疫细胞上的PD-L1表达，以评估与新辅助durvalumab联合化疗在TNBC中的获益的相关性。从参加I/II期临床试验（NCT 02489448）的患者中获得治疗前空芯针活检（n=69）。由于技术问题和组织不足，最终分析纳入了45例患者（pCR = 18例，非pCR = 27例）。使用先前验证的基于Ultivue DNA的Ultimapper®试剂盒（CD 8、CD 68、PD-L1、细胞角蛋白/Sox 10和Hoechst复染剂）对载玻片进行染色。使用AQUA软件（版本3.2.2.1），通过分子区室化（无分割）分析三个组织区室（包括肿瘤（细胞角蛋白阳性细胞）、CD 68阳性细胞和整体基质）中的PD-L1表达。在pCR患者中，与非pCR患者相比，肿瘤细胞、CD 68阳性细胞和间质中的PD-L1表达显著更高。在pCR和非pCR病例之间，肿瘤或间质区室中的CD 68阳性细胞数量无差异。PD-L1在肿瘤细胞、间质免疫细胞中的表达以及与CD 68阳性细胞共定位与TNBC中durvalumab和化疗的pCR率较高相关。
In both the IMpassion 130 trial in the metastatic setting and in Keynote 522 in the neoadjuvant setting, triple negative breast cancer (TNBC) patients 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. Pre-treatment core needle biopsies (n=69) were obtained from patients who participated in a Phase I/II clinical trial (NCT02489448). The final analysis included 45 patients (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 positive cells, and overall stroma. In patients with pCR, PD-L1 expression was significantly higher in tumor cells, in CD68 positive cells and in the stroma compared to patients non-pCR. There was no difference in the amount of CD68 positive 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 co-localized with CD68 positive cells is associated with higher rates of pCR to durvalumab and chemotherapy in TNBC.