Immune checkpoint inhibitor therapies targeting PD-1/PD-L1 are now the standard of care in oncology across several hematologic and solid tumor types, including triple negative breast cancer (TNBC). Patients with metastatic or locally advanced TNBC with PD-L1 expression on immune cells occupying ≥1% of tumor area demonstrated survival benefit with the addition of atezolizumab to nab-paclitaxel. However, concerns regarding variability between immunohistochemical PD-L1 assay performance and inter-reader reproducibility have been raised. High tumor-infiltrating lymphocytes (TILs) have also been associated with response to PD-1/PD-L1 inhibitors in patients with breast cancer (BC). TILs can be easily assessed on hematoxylin and eosin-stained slides and have shown reliable inter-reader reproducibility. As an established prognostic factor in early stage TNBC, TILs are soon anticipated to be reported in daily practice in many pathology laboratories worldwide. Because TILs and PD-L1 are parts of an immunological spectrum in BC, we propose the systematic implementation of combined PD-L1 and TIL analyses as a more comprehensive immuno-oncological biomarker for patient selection for PD-1/PD-L1 inhibition-based therapy in patients with BC. Although practical and regulatory considerations differ by jurisdiction, the pathology community has the responsibility to patients to implement assays that lead to optimal patient selection. We propose herewith a risk-management framework that may help mitigate the risks of suboptimal patient selection for immuno-therapeutic approaches in clinical trials and daily practice based on combined TILs/PD-L1 assessment in BC. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

中文翻译：

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更好的生物标志物之路：应用风险管理框架将 PD-L1 和 TIL 作为乳腺癌临床试验和日常实践中的免疫肿瘤生物标志物。


针对 PD-1/PD-L1 的免疫检查点抑制剂疗法现已成为多种血液学和实体瘤类型（包括三阴性乳腺癌 (TNBC)）的肿瘤学护理标准。免疫细胞上表达 PD-L1 且肿瘤面积占 ≥1% 的转移性或局部晚期 TNBC 患者在白蛋白结合型紫杉醇中添加 atezolizumab 后显示出生存获益。然而，人们对免疫组织化学 PD-L1 检测性能和读者间重现性之间的变异性表示担忧。高肿瘤浸润淋巴细胞 (TIL) 也与乳腺癌 (BC) 患者对 PD-1/PD-L1 抑制剂的反应相关。 TIL 可以在苏木精和伊红染色的载玻片上轻松评估，并显示出可靠的读者间重现性。作为早期 TNBC 的既定预后因素，预计很快就会在全球许多病理实验室的日常实践中报告 TIL。由于 TIL 和 PD-L1 是 BC 免疫学谱的一部分，因此我们建议系统地实施 PD-L1 和 TIL 组合分析，作为更全面的免疫肿瘤生物标志物，用于基于 PD-1/PD-L1 抑制的患者选择BC 患者的治疗。尽管实际和监管方面的考虑因司法管辖区而异，但病理学界有责任对患者实施导致最佳患者选择的检测。我们在此提出一个风险管理框架，该框架可能有助于降低基于 BC 的 TIL/PD-L1 联合评估的临床试验和日常实践中免疫治疗方法选择次优患者的风险。 © 2020 大不列颠及爱尔兰病理学会。由约翰·威利父子有限公司出版