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  • [Int J Radiat Oncol Biol Phys .] Association of T Cell Senescence with Radiation Pneumonitis in Patients with Non-small Cell Lung Cancer비소세포성폐암 환자에서 방사선 폐렴 과 T세포 노화와의 연관성

    KAIST, 성균관의대 / 김경환, 표홍렬, 신의철*, 안명주*

  • 출처
    Int J Radiat Oncol Biol Phys .
  • 등재일
    2023 Feb 1
  • 저널이슈번호
    115(2):464-475.
  • 내용

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    Abstract
    Purpose: Associations between immunosenescence and radiation pneumonitis (RP) are largely unknown. We aimed to identify a peripheral blood T cell senescence biomarker to predict RP in patients with non-small cell lung cancer (NSCLC).

    Methods and materials: Patients with locally advanced NSCLC who received definitive concurrent chemoradiotherapy (dCRT) were prospectively registered (cohort 1, n=23; cohort 2, n=31). Peripheral blood was collected at baseline, during dCRT, and at 1 month post-dCRT. Patients were dichotomized to grade ≥2 (G2+) RP and grade 0-1 (G0-1) RP. Flow cytometry was performed to assess phenotypes and functional properties of T cell subsets. RP incidence was estimated via competing risk analysis.

    Results: Five and six patients exhibited G2+ RP following dCRT in cohorts 1 and 2, respectively. Patients with G2+ RP exhibited a more aged T cell pool and higher frequencies of senescent CD57+CD28-CD8+ T cells than patients with G0-1 RP at baseline, during dCRT, and at 1 month post-dCRT. These senescent cells exhibited increased granzyme B, IFN-γ, and TNF-α production. Higher baseline frequency of CD57+CD28-CD8+ T cells was an independent predictor of G2+ RP (hazard ratio, 8.42; 95% confidence interval, 2.58-27.45; P<0.001). Recursive partitioning analysis revealed three distinct risk groups stratified by baseline CD57+CD28-CD8+ T cell frequency and lung V20 Gy, with 1-year cumulative G2+ RP incidences of 50.0%, 16.7%, and 0% for high-, intermediate-, and low-risk groups, respectively (P=0.002).

    Conclusions: Higher baseline frequencies of CD57+CD28-CD8+ T cells correlated with increased G2+ RP risks. Our results suggest the need for further investigation of the role of T cell senescence on radiation-induced organ damage.

     

     

    Affiliations

    Kyung Hwan Kim 1, Hongryull Pyo 2, Hoyoung Lee 3, Dongryul Oh 2, Jae Myoung Noh 2, Yong Chan Ahn 2, Chang Gon Kim 4, Hong In Yoon 1, Jiyun Lee 5, Sehhoon Park 6, Hyun-Ae Jung 6, Jong-Mu Sun 6, Se-Hoon Lee 6, Jin Seok Ahn 6, Keunchil Park 6, Bo Mi Ku 7, Eui-Cheol Shin 8, Myung-Ju Ahn 9
    1Department of Radiation Oncology, Yonsei Cancer Center, Heavy Ion Therapy Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.
    2Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
    3Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
    4Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
    5Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
    6Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
    7Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
    8Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea. Electronic address: ecshin@kaist.ac.kr.
    9Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. Electronic address: silkahn@skku.edu.

  • 키워드
    T cell senescence; chemoradiotherapy; non-small cell lung cancer; peripheral blood; radiation pneumonitis.
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