Immune Activation and a 9-Year Ongoing Complete Remission Following CD40 Antibody Therapy and Metastasectomy in a Patient with Metastatic Melanoma
Immune Activation and a 9-Year Ongoing Complete Remission Following CD40 Antibody Therapy and Metastasectomy in a Patient with Metastatic Melanoma
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DOI：
10.1158/2326-6066.cir-14-0154
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发表时间：
2014-11-01
影响因子：
10.1
通讯作者：
Vonderheide, Robert H.
中科院分区：
文献类型：
--
作者：
Bajor, David L.;Xu, Xiaowei;Vonderheide, Robert H.
通过激动性mAb的直接免疫激活是对癌症中抑制性免疫受体的治疗性阻断的潜在补充方法。在这里，我们提供了与使用激动性CD40 mAb的转移性黑色素瘤患者的免疫学后果的遗传分析，该患者接受了单次膀胱切除术，然后在开始治疗后持续9年以上达到完全缓解。免疫治疗后的肿瘤微环境与促炎性调节和新生T细胞库的出现相关，如通过肿瘤和血液中T细胞受体（TCR）的下一代测序所检测到的。在治疗后乳腺切除术样本中发现的从头T细胞库在治疗完成后的循环中也存在，并且在某些情况下扩大。对这种“特殊应答者”的全面研究突出了直接免疫激动剂在下一波癌症免疫治疗中的潜在潜力，以及TCR深度测序在癌症免疫评估中的潜在作用。(C)2014年AACR。
Direct immune activation via agonistic mAbs is a potentially complementary approach to therapeutic blockade of inhibitory immune receptors in cancer. Here, we provide genetic analysis of the immunologic consequences associated with the use of an agonistic CD40 mAb in a patient with metastatic melanoma who responded, underwent a single metastasectomy, and then achieved a complete remission ongoing for more than 9 years after starting therapy. Tumor microenvironment after immunotherapy was associated with proinflammatory modulations and emergence of a de novo T-cell repertoire as detected by next-generation sequencing of T-cell receptors (TCR) in the tumor and blood. The de novo T-cell repertoire identified in the posttreatment metastasectomy sample was also present-and in some cases expanded-in the circulation years after completion of therapy. Comprehensive study of this "exceptional responder" highlights the emerging potential of direct immune agonists in the next wave of cancer immunotherapies and a potential role for TCR deep sequencing in cancer immune assessment. (C) 2014 AACR.