Oncology Biomarker Development.
Bioinformatics, and.
Blood Adv. 2019 Feb 26;3(4):531-540. doi: 10.1182/bloodadvances.2018020602.
Programmed death-ligand 1 (PD-L1) and its receptor, programmed cell death-1 (PD-1), are important negative regulators of immune cell activation. Therapeutically targeting PD-1/PD-L1 in diffuse large B-cell lymphoma (DLBCL) patients with a single agent has limited activity, meriting a deeper understanding of this complex biology and of available PD-L1 clinical assays. In this study, we leveraged 2 large de novo DLBCL phase 3 trials (GOYA and MAIN) to better understand the biologic and clinical relevance of PD-L1 in de novo DLBCL. PD-L1 was expressed on myeloid cells in 85% to 95% of DLBCL patients (depending on staining procedure), compared with 10% on tumor cells, and correlated with macrophage gene expression. PD-L1 did not identify high-risk patients in de novo DLBCL; it correlated with , macrophage gene expression, and improved outcomes among a subset of patients. These results may help identify immunologically distinct DLBCL subsets relevant for checkpoint blockade. GOYA and MAIN trials were registered at www.clinicaltrials.gov as #NCT01287741 and #NCT00486759, respectively.
程序性死亡配体 1（PD-L1）及其受体程序性细胞死亡蛋白 1（PD-1）是免疫细胞激活的重要负性调节因子。在弥漫性大 B 细胞淋巴瘤（DLBCL）患者中，使用单一药物靶向 PD-1/PD-L1 的治疗活性有限，这需要更深入地了解这一复杂的生物学和现有的 PD-L1 临床检测方法。在这项研究中，我们利用两项大型的原发弥漫性大 B 细胞淋巴瘤 3 期临床试验（GOYA 和 MAIN），以更好地理解 PD-L1 在原发弥漫性大 B 细胞淋巴瘤中的生物学和临床相关性。PD-L1 在 85%至 95%的弥漫性大 B 细胞淋巴瘤患者（取决于染色程序）的髓系细胞上表达，而在肿瘤细胞上表达 10%，与巨噬细胞基因表达相关。PD-L1 并未在原发弥漫性大 B 细胞淋巴瘤中识别出高危患者；它与巨噬细胞基因表达相关，并改善了部分患者的预后。这些结果可能有助于识别与检查点阻断相关的免疫上不同的弥漫性大 B 细胞淋巴瘤亚群。GOYA 和 MAIN 试验分别在 www.clinicaltrials.gov 上注册为 #NCT01287741 和 #NCT00486759。
