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Immunological Characteristics of Hyperprogressive Disease in Patients with Non-small Cell Lung Cancer Treated with Anti-PD-1/PD-L1 Abs

  • Kyung Hwan Kim (Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine) ;
  • Joon Young Hur (Division of Hematology and Oncology, Department of Internal Medicine, Hanyang University Guri Hospital) ;
  • Jiae Koh (Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Jinhyun Cho (Division of Hematology-Oncology, Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine) ;
  • Bo Mi Ku (Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • June Young Koh (Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST)) ;
  • Jong-Mu Sun (Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Se-Hoon Lee (Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Jin Seok Ahn (Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Keunchil Park (Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Myung-Ju Ahn (Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University) ;
  • Eui-Cheol Shin (Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST))
  • Received : 2020.08.12
  • Accepted : 2020.12.08
  • Published : 2020.12.31
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Abstract

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 CD39+CD8+ 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.

Keywords

Acknowledgement

This study was supported by the National Research Foundation (grant NRF-2018M3A9D3079498), which is funded by the Ministry of Science and ICT.

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