Gopalakrishnan Dharmesh, Jain Rohit K, Herbst Laurie, Sikorski Marcus, Mandava Silpa, Azabdaftari Gissou, Xu Bo, LeVea Charles, Robillard Kevin, Ernstoff Marc S, George Saby
Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States.
Department of Genitourinary Oncology, Moffitt Cancer Center and Research Institute, Tampa, FL, United States.
Front Oncol. 2021 Apr 29;11:679177. doi: 10.3389/fonc.2021.679177. eCollection 2021.
Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. Nivolumab, an anti-PD-1 monoclonal antibody, markedly improved overall survival in advanced renal cell carcinoma (RCC). However, ICIs can rarely trigger massive inflammation, a phenomenon characterized by rapid acceleration in radiographic tumor growth, the mechanisms underlying which are largely unknown. We report three patients with metastatic RCC who experienced rapid radiographic progression and clinical deterioration following treatment with nivolumab. However, histological analysis revealed no viable cancer despite the evidence of radiological progression. Instead, extensive necrosis and lymphohistiocytic infiltration were noted, as described previously in patients with ICI-induced pseudoprogression. Based on these observations, we postulate that exuberant antitumor inflammatory responses may contribute to adverse clinical outcomes in some patients with ICI-induced radiographic progression. Prospective studies incorporating tumor biopsies may shed more light on this rare phenomenon.
免疫检查点抑制剂（ICIs）彻底改变了癌症治疗方式。纳武单抗，一种抗程序性死亡蛋白1（PD-1）单克隆抗体，显著提高了晚期肾细胞癌（RCC）患者的总生存率。然而，ICIs很少能引发大规模炎症，这一现象的特征是影像学上肿瘤生长迅速加速，其潜在机制在很大程度上尚不清楚。我们报告了3例转移性RCC患者，他们在接受纳武单抗治疗后出现了影像学上的快速进展和临床恶化。然而，组织学分析显示，尽管有放射学进展的证据，但未发现存活的癌细胞。相反，如先前在ICI诱导的假性进展患者中所描述的那样，观察到广泛的坏死和淋巴细胞组织细胞浸润。基于这些观察结果，我们推测，在一些ICI诱导的影像学进展患者中，过度的抗肿瘤炎症反应可能导致不良临床结局。纳入肿瘤活检的前瞻性研究可能会更清楚地揭示这一罕见现象。
