Robert W. Franz Cancer Research Center, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, Oregon.
Cancer Immunol Res. 2016 Aug;4(8):650-7. doi: 10.1158/2326-6066.CIR-16-0022. Epub 2016 Jun 4.
Immune checkpoint inhibitors are transforming the way cancer is treated. However, these therapies do not benefit all patients and frequently cause significant immune-related adverse events. Biomarkers that identify patients with a favorable early response to therapy are essential for guiding treatment decisions and improving patient outcomes. In this report of our study, we present evidence that shortly after administration of dual PD-1/CTLA-4 blockade, the proinflammatory capacity of peripheral lymphocytes is predictive of tumor progression and survival outcomes in multiple murine models. Specifically, we observed that the quantity of interferon-γ (IFNγ) produced by peripheral lymphocytes in response to CD3/CD28 stimulation was robustly correlated with subsequent survival outcomes. In the tumor models and early time points assessed in this study, this relationship was considerably more predictive than a host of other potential biomarkers, several of which have been previously reported. Overall, these findings suggest that measuring the capacity of peripheral lymphocytes to produce IFNγ may help identify which patients are benefitting from combination anti-PD-1/anti-CTLA-4 immunotherapy. Cancer Immunol Res; 4(8); 650-7. ©2016 AACR.
免疫检查点抑制剂正在改变癌症的治疗方式。然而，这些疗法并非对所有患者都有效，而且经常会引起严重的免疫相关不良反应。识别对治疗有早期有利反应的患者的生物标志物对于指导治疗决策和改善患者预后至关重要。在我们的研究报告中，我们提供了证据，表明在接受 PD-1/CTLA-4 双重阻断后不久，外周淋巴细胞的促炎能力可预测多种小鼠模型中的肿瘤进展和生存结局。具体而言，我们观察到外周淋巴细胞在 CD3/CD28 刺激下产生的干扰素-γ (IFNγ) 的数量与后续的生存结局具有很强的相关性。在本研究评估的肿瘤模型和早期时间点中，这种关系比许多其他潜在的生物标志物更具预测性，其中一些先前已有报道。总体而言，这些发现表明，测量外周淋巴细胞产生 IFNγ 的能力可能有助于识别哪些患者从抗 PD-1/抗 CTLA-4 联合免疫疗法中获益。Cancer Immunol Res; 4(8); 650-7. ©2016 AACR.
