Kim Kyung Hwan, Hur Joon Young, Koh Jiae, Cho Jinhyun, Ku Bo Mi, Koh June Young, Sun Jong-Mu, Lee Se-Hoon, Ahn Jin Seok, Park Keunchil, Ahn Myung-Ju, Shin Eui-Cheol
Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul 03722, Korea.
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea.
Immune Netw. 2020 Dec 21;20(6):e48. doi: 10.4110/in.2020.20.e48. eCollection 2020 Dec.
Hyperprogressive disease (HPD) is a distinct pattern of progression characterized by acceleration of tumor growth after treatment with anti-PD-1/PD-L1 Abs. However, the immunological characteristics have not been fully elucidated in patients with HPD. We prospectively recruited patients with metastatic non-small cell lung cancer treated with anti-PD-1/PD-L1 Abs between April 2015 and April 2018, and collected peripheral blood before treatment and 7-days post-treatment. HPD was defined as ≥2-fold increase in both tumor growth kinetics and tumor growth rate between pre-treatment and post-treatment. Peripheral blood mononuclear cells were analyzed by multi-color flow cytometry to phenotype the immune cells. Of 115 patients, 19 (16.5%) developed HPD, 52 experienced durable clinical benefit (DCB; partial response or stable disease ≥6 months), and 44 experienced non-hyperprogressive progression (NHPD). Patients with HPD had significantly lower progression-free survival (p<0.001) and overall survival (p<0.001). When peripheral blood immune cells were examined, the pre-treatment frequency of CD39 cells among CD8 T cells was significantly higher in patients with HPD compared to those with NHPD, although it showed borderline significance to predict HPD. Other parameters regarding regulatory T cells or myeloid derived suppressor cells did not significantly differ among patient groups. Our findings suggest high pre-treatment frequency of CD39CD8 T cells might be a characteristic of HPD. Further investigations in a larger cohort are needed to confirm our results and better delineate the immune landscape of HPD.
超进展性疾病（HPD）是一种独特的疾病进展模式，其特征为使用抗PD-1/PD-L1抗体治疗后肿瘤生长加速。然而，HPD患者的免疫学特征尚未完全阐明。我们前瞻性招募了2015年4月至2018年4月期间接受抗PD-1/PD-L1抗体治疗的转移性非小细胞肺癌患者，并在治疗前和治疗后7天采集外周血。HPD定义为治疗前与治疗后肿瘤生长动力学和肿瘤生长速率均增加≥2倍。通过多色流式细胞术分析外周血单个核细胞以对免疫细胞进行表型分析。在115例患者中，19例（16.5%）发生HPD，52例经历持久临床获益（DCB；部分缓解或疾病稳定≥6个月），44例经历非超进展性进展（NHPD）。HPD患者的无进展生存期（p<0.001）和总生存期（p<0.001）显著更低。检查外周血免疫细胞时，与NHPD患者相比，HPD患者中CD8 T细胞中CD39细胞的治疗前频率显著更高，尽管其对预测HPD仅显示临界显著性。关于调节性T细胞或髓源性抑制细胞的其他参数在患者组之间无显著差异。我们的研究结果表明，CD39+CD8 T细胞的高治疗前频率可能是HPD的一个特征。需要在更大队列中进行进一步研究以证实我们的结果并更好地描绘HPD的免疫格局。
