Combining immune checkpoint inhibitors with other treatments likely to harness tumor immunity is a rising strategy in oncology. The exact modalities of such a combinatorial regimen are yet to be defined, and most attempts have relied so far on concomitant dosing, rather than sequential or phased administration. Because immunomodulating features are likely to be time-, dose-, and-schedule dependent, the need for biomarkers providing real-time information is critical to better define the optimal time-window to combine immune checkpoint inhibitors with other drugs. In this review, we present the various putative markers that have been investigated as predictive tools with immune checkpoint inhibitors and could be used to help further combining treatments. Whereas none of the current biomarkers, such as the PDL1 expression of a tumor mutational burden, is suitable to identify the best way to combine treatments, monitoring circulating tumor DNA is a promising strategy, in particular to check whether the STING-cGAS pathway has been activated by cytotoxics. As such, circulating tumor DNA could help defining the best time-window to administrate immune checkpoint inhibitors after that cytotoxics have been given.

中文翻译：

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像滚石一样：Sting-Cgas通路和无细胞DNA作为组合免疫治疗的生物标记。

将免疫检查点抑制剂与可能利用肿瘤免疫力的其他治疗方法相结合是肿瘤学中的一项新兴战略。这种组合方案的确切方式尚待确定，到目前为止，大多数尝试都依赖于同时给药，而不是顺序或分阶段给药。由于免疫调节功能可能会随时间，剂量和时间表而变，因此对提供实时信息的生物标志物的需求对于更好地定义将免疫检查点抑制剂与其他药物结合的最佳时间窗口至关重要。在这篇综述中，我们介绍了各种推定的标记物，这些标记物已与免疫检查点抑制剂一起用作预测工具，可用于帮助进一步组合治疗。鉴于目前没有任何生物标志物，例如肿瘤突变负担的PDL1表达，适用于确定最佳的组合治疗方法，监测循环肿瘤DNA是一种有前途的策略，尤其是检查STING-cGAS途径是否已被细胞毒素激活。这样，循环肿瘤DNA可以帮助确定在给予细胞毒性后给予免疫检查点抑制剂的最佳时间窗口。