López José I, Pulido Rafael, Cortés Jesús M, Angulo Javier C, Lawrie Charles H
Department of Pathology, Cruces University Hospital, Barakaldo, Spain; Biomarkers in Cancer Unit, Biocruces Research Institute, Barakaldo, Spain; Department of Medical-Surgical Specialties, University of the Basque Country (UPV/EHU), Leioa, Spain.
Biomarkers in Cancer Unit, Biocruces Research Institute, Barakaldo, Spain; IKERBASQUE, The Basque Foundation for Science, Bilbao, Spain.
Pathol Res Pract. 2018 Aug;214(8):1110-1114. doi: 10.1016/j.prp.2018.06.003. Epub 2018 Jun 12.
Intratumor heterogeneity (ITH) detection remains a challenge in modern oncology because it can have a direct impact on the success of new therapies. Anti-PD-1/PD-L1 immunotherapy is an emerging treatment modality that is showing great promise for clear cell renal cell carcinoma (CCRCC) patients with advanced disease. Patient selection for such therapy relies upon the immunohistochemical detection of PD-1/PD-L1, however the degree of ITH for these markers among tumor cells and/or inflammatory mononuclear infiltrates remains unknown. Therefore, we analyzed PD-L1 (SP-142) expression in the tumor inflammatory cells of 22 CCRCC cases with the aim to define the pattern of PD-L1 expression, and to compare the reliability of current tumor sampling protocols (RS) with a multisite tumor sampling strategy (MSTS). While the RS protocol identified 5/22 (22.7%) of cases that were positive for PD-L1 expression, MSTS identified 10/22 (45.45%) of cases. This suggests that RS may miss a proportion of CCRCC patients that might benefit from immunotherapy. In addition, MSTS demonstrated that positive and negative regions of PD-L1 expression are very variable within each tumor.
肿瘤内异质性（ITH）检测在现代肿瘤学中仍然是一项挑战，因为它会直接影响新疗法的成效。抗PD-1/PD-L1免疫疗法是一种新兴的治疗方式，对晚期透明细胞肾细胞癌（CCRCC）患者显示出巨大潜力。此类疗法的患者选择依赖于PD-1/PD-L1的免疫组化检测，然而肿瘤细胞和/或炎性单核浸润中这些标志物的ITH程度仍不清楚。因此，我们分析了22例CCRCC病例肿瘤炎性细胞中PD-L1（SP-142）的表达，目的是确定PD-L1的表达模式，并比较当前肿瘤取样方案（RS）与多部位肿瘤取样策略（MSTS）的可靠性。RS方案确定5/22（22.7%）的病例PD-L1表达呈阳性，而MSTS确定10/22（45.45%）的病例呈阳性。这表明RS可能会遗漏一部分可能从免疫疗法中获益的CCRCC患者。此外，MSTS表明每个肿瘤内PD-L1表达的阳性和阴性区域差异很大。
