Department of Oncology, West China Hospital, Sichuan University, Chengdu, China.
The Medical Department, 3D Medicines Inc., Shanghai, China.
Front Immunol. 2021 Sep 29;12:749204. doi: 10.3389/fimmu.2021.749204. eCollection 2021.
Microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) status of tumors is a distinct predictive biomarker of immune checkpoint inhibitors (ICIs) for colorectal and non-colorectal cancer populations. The overall response rate (ORR) varies from approximately 40% to 60%, indicating that nearly half of MSI-H tumors do not respond to ICIs. The mechanism of response heterogeneity in MSI-H/dMMR cancers is unclear. Some patients who have been treated with ICIs have developed a novel pattern of progression called hyperprogression, which is defined as unexpected accelerated tumor growth. No case of MSI-H/dMMR immunotherapy-associated hyperprogression has been reported in the literature. Here, we present the case of a patient with dMMR gastrointestinal cancer who suffered hyperprogressive disease (HPD) after treatment with nivolumab. We explored the potential mechanisms of HPD by clinical, immune, and genomic characteristics. Extremely high levels of serum LDH, low TMB and TILs, and the disruption of TGFβ signaling, may be related to hyperprogression.
肿瘤微卫星不稳定性高/错配修复缺陷（MSI-H/dMMR）状态是结直肠癌和非结直肠癌人群免疫检查点抑制剂（ICIs）的一个显著预测生物标志物。总体反应率（ORR）从大约 40%到 60%不等，这表明近一半的 MSI-H 肿瘤对 ICIs 没有反应。MSI-H/dMMR 癌症反应异质性的机制尚不清楚。一些接受 ICI 治疗的患者出现了一种新的进展模式，称为超进展，定义为意外的加速肿瘤生长。在文献中尚未报道 MSI-H/dMMR 免疫治疗相关的超进展病例。在这里，我们报告了一例接受nivolumab 治疗的 dMMR 胃肠道癌患者发生超进展性疾病（HPD）的病例。我们通过临床、免疫和基因组特征探讨了 HPD 的潜在机制。极高水平的血清 LDH、低 TMB 和 TILs 以及 TGFβ 信号通路的破坏可能与超进展有关。
