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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

Immune Network 2020년 20권 6호 p.48 ~ 48
김경환, 허준영, 고지애, 조진현, 구보미, 고준영, 선종무, 이세훈, 안진석, 박근칠, 안명주, 신의철,
소속 상세정보
김경환 ( Kim Kyung-Hwan ) - Yonsei University College of Medicine Department of Radiation Oncology
허준영 ( Hur Joon-Young ) - Hanyang University Guri Hospital Department of Internal Medicine
고지애 ( Koh Ji-Ae ) - Sungkyunkwan University School of Medicine Samsung Medical Center Research Institute for Future Medicine
조진현 ( Cho Jin-Hyun ) - Inha University School of Medicine Inha University Hospital Department of Internal Medicine
구보미 ( Ku Bo-Mi ) - Sungkyunkwan University School of Medicine Samsung Medical Center Research Institute for Future Medicine
고준영 ( Koh June-Young ) - Korea Advanced Institute of Science and Technology Graduate School of Medical Science and Engineering
선종무 ( Sun Jong-Mu ) - Sungkyunkwan University School of Medicine Samsung Medical Center Department of Medicine
이세훈 ( Lee Se-Hoon ) - Sungkyunkwan University School of Medicine Samsung Medical Center Department of Medicine
안진석 ( Ahn Jin-Seok ) - Sungkyunkwan University School of Medicine Samsung Medical Center Department of Medicine
박근칠 ( Park Keun-Chil ) - Sungkyunkwan University School of Medicine Samsung Medical Center Department of Medicine
안명주 ( Ahn Myung-Ju ) - Sungkyunkwan University School of Medicine Samsung Medical Center Department of Medicine
신의철 ( Shin Eui-Cheol ) - Korea Advanced Institute of Science and Technology Graduate School of Medical Science and Engineering

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.

키워드

Hyperprogressive disease; PD-1-PD-L1 blockade; Lung cancer; Peripheral blood human mononuclear cells; CD39; T cell

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