Ludwig Center for Metastasis Research, The University of Chicago, Chicago, Illinois, USA.
Mol Ther. 2012 May;20(5):1046-55. doi: 10.1038/mt.2012.19. Epub 2012 Feb 14.
Radiotherapy offers an effective treatment for advanced cancer but local and distant failures remain a significant challenge. Here, we treated melanoma and pancreatic carcinoma in syngeneic mice with ionizing radiation (IR) combined with the poly(ADP-ribose) polymerase inhibitor (PARPi) veliparib to inhibit DNA repair and promote accelerated senescence. Based on prior work implicating cytotoxic T lymphocytes (CTLs) as key mediators of radiation effects, we discovered that senescent tumor cells induced by radiation and veliparib express immunostimulatory cytokines to activate CTLs that mediate an effective antitumor response. When these senescent tumor cells were injected into tumor-bearing mice, an antitumor CTL response was induced which potentiated the effects of radiation, resulting in elimination of established tumors. Applied to human cancers, radiation-inducible immunotherapy may enhance radiotherapy responses to prevent local recurrence and distant metastasis.
放射治疗为晚期癌症提供了一种有效的治疗方法，但局部和远处失败仍然是一个重大挑战。在这里，我们用电离辐射（IR）联合聚（ADP-核糖）聚合酶抑制剂（PARPi）维利帕尼治疗同源小鼠的黑色素瘤和胰腺癌，以抑制 DNA 修复并促进加速衰老。基于先前的工作表明细胞毒性 T 淋巴细胞（CTLs）是放射效应的关键介质，我们发现放射和维利帕尼诱导的衰老肿瘤细胞表达免疫刺激性细胞因子，激活介导有效抗肿瘤反应的 CTLs。当将这些衰老的肿瘤细胞注射到荷瘤小鼠中时，会诱导抗肿瘤 CTL 反应，从而增强放射治疗的效果，导致已建立的肿瘤消除。应用于人类癌症，放射诱导免疫疗法可能增强放疗反应，以防止局部复发和远处转移。
