RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:A case report of hemophagocytic lymphohistiocytosis induced by toripalimab plus chemoradiotherapy in cervical cancer.
A case report of hemophagocytic lymphohistiocytosis induced by toripalimab plus chemoradiotherapy in cervical cancer.
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背景:噬血细胞性淋巴组织细胞增多症(HLH)是罕见但可危及生命的免疫过度活化综合征。免疫检查点抑制剂相关HLH报道有限,诊疗指南不足。本文首次报告局部晚期宫颈癌患者发生PD-1抑制剂相关HLH并成功处理。病例为47岁FIGO IIIC1r期患者,接受特瑞普利单抗联合放化疗后出现发热、脾大、白细胞减少、贫血、血小板减少、高甘油三酯、低纤维蛋白原、高铁蛋白、NK细胞活性降低、可溶性CD25升高及骨髓噬血现象。患者接受甲泼尼龙后成功治疗,目前存活且肿瘤完全缓解。接受免疫检查点抑制剂患者若出现难治性发热、血细胞减少和脾大,应考虑HLH以便早期识别罕见毒性。多学科治疗有助于及时诊断和控制,避免组织损伤及器官衰竭。糖皮质激素单药治疗免疫相关HLH的作用仍需研究。
Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening clinical syndrome characterized by immune hyperactivation. Unlike primary HLH, immune checkpoint inhibitor (ICI)-triggered HLH is not well described, and there is a lack of theranostic guidelines. Herein, we first reported the successful management of PD-1 inhibitor-associated HLH in locally advanced cervical cancer. CASE PRESENTATION: We report a case of HLH in a 47-year-old patient with International Federation of Gynecology and Obstetrics (FIGO) IIIC1r cervical cancer who received toripalimab, a programmed cell death-1 receptor inhibitor, combined with chemoradiotherapy. The patient developed pyrexia, splenomegaly, leukopenia, anemia, thrombocytopenia, hypertriglyceridemia, hypofibrinogenemia, hyperferritinemia, reduced NK cell activity, elevated sCD25 levels, and hemophagocytosis in a bone marrow aspirate. Our patient was successfully treated with methylprednisolone, indicating that immune-induced HLH might respond to glucocorticoids, and is still alive with a complete response of the tumor.
Considering the possibility of HLH is needed in patients receiving ICIs to detect rare toxicities at an early stage when the patient develops uncontrollable fever, cytopenia, and splenomegaly, our multidisciplinary treatment modality contributed to the early diagnosis and successful management of HLH, avoiding progressive tissue damage and organ failure. Whether glucocorticoids are used alone or not for immune-associated HLH needs further investigation.
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