Department of Pathology, School of Medicine, Sapporo Medical University, Sapporo, Japan.
Department of Surgical Pathology, Sapporo Medical University Hospital, Sapporo, Japan.
Immunol Med. 2021 Jun;44(2):136-141. doi: 10.1080/25785826.2020.1788229. Epub 2020 Jul 7.
Effective management of immune-related adverse events in patients receiving immunotherapy for cancer is problematic. In this report, we present the case of a 58-year-old man with advanced clear cell renal cell carcinoma who responded well to a combination of ipilimumab and nivolumab. However, after two courses of treatment, he developed fulminant hepatitis and died. An autopsy confirmed that the primary lesion in the left kidney was more than 99% necrotic with only six small residual tumor lesions. These lesions were infiltrated by large numbers of CD8-positive/TIA-1-positive lymphocytes. However, a metastatic lesion in the right kidney harbored few lymphocytes. Furthermore, the tumor cells in the metastatic lesion and one of the residual lesions showed decreased expression of HLA class I molecules, which are a prerequisite for cytotoxic T-lymphocyte-mediated immunotherapy in tumor cells. In this patient, more than 80% of hepatocytes were destroyed and the parenchyma was infiltrated with CD8-positive/TIA-1-positive lymphocytes. The patient had polyuria, which was attributed to neurohypophysitis caused by the infiltration of CD8-positive/TIA-1-positive lymphocytes. We believe that this is an instructive case for immuno-oncologists.
有效管理癌症免疫治疗患者的免疫相关不良反应是一个问题。在本报告中，我们报告了一例 58 岁的晚期透明细胞肾细胞癌患者，他对伊匹单抗和纳武单抗联合治疗反应良好。然而，在两个疗程后，他发生暴发性肝炎并死亡。尸检证实左肾的原发性病变有 99%以上坏死，只有 6 个小的残留肿瘤病变。这些病变被大量 CD8 阳性/TIA-1 阳性淋巴细胞浸润。然而，右肾的转移病变中淋巴细胞较少。此外，转移病变和一个残留病变中的肿瘤细胞 HLA Ⅰ类分子表达减少，这是肿瘤细胞中细胞毒性 T 淋巴细胞介导的免疫治疗的前提。在该患者中，超过 80%的肝细胞被破坏，实质被 CD8 阳性/TIA-1 阳性淋巴细胞浸润。患者有多尿，这归因于 CD8 阳性/TIA-1 阳性淋巴细胞浸润引起的神经垂体炎。我们认为这是免疫肿瘤学家的一个有启发性的病例。
