Institute for Computer Science and Control (SZTAKI), Kende u 13-17, Budapest, 1111, Hungary.
Brigham and Women's Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA, 02115, USA.
Cancer Immunol Immunother. 2020 May;69(5):683-687. doi: 10.1007/s00262-020-02543-6. Epub 2020 Mar 9.
More than 2000 immuno-oncology agents are being tested or are in use as a result of the cancer immunotherapy revolution. Manipulation of co-inhibitory receptors has achieved tumor eradication in a minority of patients, but widespread immune-related adverse events (irAEs) compromised tolerance to healthy self-tissues in the majority. We have proposed that a major mechanism of irAEs is similar to a graft-versus-malignancy effect of graft-versus-host disease. To verify our hypothesis, we retrieved post-marketing data of adverse events from the U.S. Food and Drug Administration Adverse Event Reporting System. A significant positive correlation was revealed in 7677 patients between the reporting odds ratio of irAEs during immune checkpoint inhibitor therapy and the corresponding tumor mutational burden across 19 cancer types. These results can be interpreted to mean that the ICI drugs unleashed T cells against "altered-self," self, and tumors resulting in better overall survival.
由于癌症免疫治疗革命，目前已有 2000 多种免疫肿瘤药物正在进行测试或已投入使用。共抑制受体的操纵在少数患者中实现了肿瘤消除，但在大多数患者中，广泛的免疫相关不良事件（irAEs）损害了对健康自身组织的耐受性。我们提出，irAEs 的一个主要机制类似于移植物抗宿主病的移植物抗恶性肿瘤效应。为了验证我们的假设，我们从美国食品和药物管理局不良事件报告系统中检索了上市后不良事件数据。在 19 种癌症类型中，我们在 7677 名接受免疫检查点抑制剂治疗的患者中发现，irAEs 的报告比值比与相应的肿瘤突变负担之间存在显著的正相关。这些结果可以解释为，ICI 药物释放针对“改变的自身”、自身和肿瘤的 T 细胞，从而导致总体生存更好。
