Tucker Matthew D, Rini Brian I
Department of Medicine, Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Cancers (Basel). 2020 Sep 18;12(9):2662. doi: 10.3390/cancers12092662.
Immunotherapy-based combinations, driven by PD-1, PD-L1, and CTLA-4 inhibitors, has altered the treatment landscape for metastatic renal cell carcinoma (RCC). Despite significant improvements in clinical outcomes, many patients do not experience deep or lasting benefits. Recent efforts to determine which patients are most likely to benefit from immunotherapy and immunotherapy-based combinations have shown promise but have not yet affected clinical practice. PD-L1 expression via immunohistochemistry (IHC) has shown promise in a few clinical trials, although variations in the IHC assays as well as the use of different values for positivity presents unique challenges for this potential biomarker. Several other candidate biomarkers were investigated including tumor mutational burden, gene expression signatures, single gene mutations, human endogenous retroviruses, the gastrointestinal microbiome, and peripheral blood laboratory markers. While individually these biomarkers have yet to explain the heterogeneity of treatment response to immunotherapy, using aggregate information from these biomarkers may inform clinically useful predictive biomarkers.
由PD-1、PD-L1和CTLA-4抑制剂驱动的基于免疫疗法的联合治疗，已经改变了转移性肾细胞癌（RCC）的治疗格局。尽管临床结果有了显著改善，但许多患者并未获得深度或持久的益处。最近确定哪些患者最有可能从免疫疗法及基于免疫疗法的联合治疗中获益的努力已显示出前景，但尚未影响临床实践。通过免疫组织化学（IHC）检测的PD-L1表达在一些临床试验中显示出前景，尽管IHC检测方法存在差异以及阳性判定值的不同，给这种潜在生物标志物带来了独特挑战。还研究了其他几种候选生物标志物，包括肿瘤突变负荷、基因表达特征、单基因突变、人类内源性逆转录病毒、胃肠道微生物群和外周血实验室标志物。虽然这些生物标志物单独来看尚未解释免疫疗法治疗反应的异质性，但利用这些生物标志物的综合信息可能有助于发现临床上有用的预测性生物标志物。
