Journal of Chest Surgery

The Korean Society for Thoracic and Cardiovascular Surgery (대한심장혈관흉부외과학회)
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Expression of CD40, CD86, and HLA-DR in CD1c+ Myeloid Dendritic Cells Isolated from Peripheral Blood in Primary Adenocarcinoma of Lung

원발성 폐선암환자의 말초혈액에서 분리한 CD1c+ 골수성 수지상 세포에서의 CD40, CD86 및 HLA-DR의 발현

  • Kang, Moon-Chul (Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital) ;
  • Kang, Chang-Hyun (Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital) ;
  • Kim, Young-Tae (Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital) ;
  • Kim, Joo-Hyun (Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital)
  • 강문철 (분당서울대학교병원 흉부외과) ;
  • 강창현 (서울대학교병원 흉부외과) ;
  • 김영태 (서울대학교병원 흉부외과) ;
  • 김주현 (서울대학교병원 흉부외과)
  • Received : 2010.04.23
  • Accepted : 2010.06.24
  • Published : 2010.10.05
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Abstract

Background: There have been several reports using animal experiments that CD1-restricted T-cells have a key role in tumor immunity. To address this issue, we studied the expression of markers for CD1c+ myeloid dendritic cells (DCs) isolated from peripheral blood in the clinical setting. Material and Method: A total of 24 patients with radiologically suspected or histologically confirmed lung cancer who underwent pulmonary resection were enrolled in this study. The patients were divided according to histology findings into three groups: primary adenocarcinoma of lung (PACL), primary squamous cell carcinoma of lung (PSqCL) and benign lung disease (BLD). We obtained 20 mL of peripheral venous blood from patients using heparin-coated syringes. Using flow-cytometry after labeling with monoclonal antibodies, data acquisition and analysis were done. Result: The ratio of CD1c+CD19- dendritic cells to CD1c+ dendritic cells were not significantly different between the three groups. CD40 (p=0.171), CD86 (p=0.037) and HLA-DR (p=0.036) were less expressed in the PACL than the BLD group. Expression of CD40 (p=0.319), CD86 (p=0.036) and HLA-DR (p=0.085) were less expressed in the PACL than the PSqCL group, but the differences were only significant for CD86. Expression of co-stimulatory markers was not different between the PSqCL and BLD groups. Expression of markers for activated DCs were dramatically lower in the PACL group than in groups with other histology (CD40 (p=0.005), CD86 (p=0.013) HLA-DR (p=0.004). Conclusion: These results suggest the possibility that CD1c+ myeloid DCs participate in control of the tumor immunity system and that low expression of markers results in lack of an immune response triggered by dendritic cells in adenocarcinoma of the lung.

배경: CD1-restricted T 세포는 동물모델실험에서 항암면역에 있어서 매우 중요한 역할을 한다는 보고가 있다. 이를 임상에서 확인하기 위해 원발성 폐선암환자의 말초혈액에 존재하는 CD1c+ 골수성 수지상 세포의 수 및 수지상 세포에서의 동시자극 표지자 중 주요 표지자인 CD40, CD86 및 HLA-DR의 발현 양상을 확인하고자 하였다. 대상 및 방법: 영상의학적으로 원발성 폐암이 의심되거나 조직학적으로 폐암으로 확진되어 외과적 폐절제 또는 생검을 시행한 총 24명의 환자를 원발성 폐선암 환자군(Primary adenocarinoma of lung, PACL)과 원발성 편병상피세포폐암군(Primary squamous cell carcinoma of lung, PSqCL) 및 양성폐질환군(Benign lung disease, BLD)군으로 나누고, 말초혈액 20 mL을 채취하여 수지상 세포를 분리하고 단일클론 항체를 이용하여 CD1c+ 골수성 세포의 수 및 수지상 세포에서의 동시자극 표지자 중 주요 표지자들의 발현정도를 유체세포측정기를 이용하여 확인하고 두 군 간의 통계적 차이 유무를 확인하였다. 결과: CD1c+ 골수성 수지상 세포(CD1c+CD19-)의 수는 PACL, PSqCL 및 BLD군 모두 그 차이가 모두 통계적으로 유의한 차이는 없었다. 공동자극표지자의 발현은 PACL군과 BLD군에서는 CD40의 발현이 p-value=0.171, CD86의 발현이 p-value=0.037과 HLA-DR의 발현이 p-value=0.036로 PACL군에서 감소한 것을 통계학적으로 확인할 수 있었다. PACL군과 PSqCL군 간에는 CD40의 발현이 p-value=0.319, CD86의 발현이 p-value= 0.036과 HLA-DR의 발현이 p-value=0.085로 PACL군에서 공동표지자의 발현이 감소한 양상이나 통계적 유의성은 CD86의 발현 외에는 없었다. PSqCL군과 BLD군간에는 공동표지자의 발현에 통계적 차이는 없었다. PACL군과 비선암군간에는 CD40의 발현이 p-value=0.005, CD86의 발현이 p-value=0.013과 HLA-DR의 발현이 p-value=0.004로 PACL군에서 공동표지자의 발현이 감소한 것을 통계학적으로 확인할 수 있었다. 결론: CD1c+ 골수성 수지상 세포에서 원발성 폐선암 환자에서 주요 표지자의 발현이 감소한 것을 확인할 수 있었으며, 이는 원발성 폐선암 환자에서 주요 표지자의 발현의 감소가 면역회피기전의 하나일 수 있는 가능성 및 수지상 세포에 의하여 유발되는 면역반응은 수지상 세포의 표지자의 발현 정도에 의해 결정된다는 가능성을 제시한다.

Keywords

References

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