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새로운 'Don’t eat me' 신호전달 분자 ‘CD24’ 역할 규명 - 바이오스펙테이터

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새로운 'Don’t eat me' 신호전달 분자 ‘CD24’ 역할 규명

입력 2019-08-05 14:50 수정 2019-08-05 17:24

바이오스펙테이터 봉나은 기자

이 기사는 '프리미엄 뉴스서비스 BioS+' 기사입니다.
암세포의 면역관문분자 'CD24'가 대식세포의 'Siglec-10'과 상호작용해 대식작용 회피..난소암 및 유방암 이종이식 마우스 모델서 ‘CD24 항체’로 생존기간 증가 확인

대식세포의 식작용을 피하는 암세포의 세 번째 면역관문분자가 밝혀졌다. 미국 스탠포드 의과대학 Irving Weissman 교수 연구팀은 암세포에서 발현되는 ‘CD24’가 종양 관련 대식세포(Tumour-associated macrophage, TAM)에서 발현하는 수용체인 'Siglec-10(Sialic-acid-binding Ig-like lectin 10)'과 상호작용해 식작용을 회피하는 면역관문분자의 역할을 한다고 발표했다. 연구 결과는 ‘CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy’를 주제로 국제학술지 ‘네이처(Nature)’에 지난달 31일 게재됐다.

이번 연구는 Weissman 교수 연구팀이 이전에 증명한 ‘CD47’과 ‘LILRB1’의 뒤를 잇는 대식세포 타깃의 새로운 면역관문분자로 주목을 받았다. T세포 타깃의 면역관문억제제 개발에 집중해왔던 지금까지의 소식과는 다른 관점이다.

일반적으로 암세포는 세포 표면에 ‘Don’t eat me’ 신호전달 분자를 과발현함으로써 면역세포의 공격을 회피하는 특성을 가지고 있다. Weissman 교수 연구팀은 암세포에서 'Don't eat me' 신호를 내는 면역관문분자 'CD47'가 대식세포의 'SIRPα(Signal-regulatory protein alpha)'와 상호작용해 면역을 회피하는 역할을 한다고 처음 규명한 바 있다. 현재 미국 포티세븐(Forty Seven), ALX 온콜로지(ALX Oncology), 중국 I-Mab 등이 CD47 항체를 이용한 다양한 임상을 진행하고 있다.

연구팀은 또한 대식세포 타깃의 두 번째 면역관문분자로 암세포에서 발현하는 ‘LILRB1’의 역할을 밝히기도 했다. 'LILRB1'은 대식세포 표면의 MHC classⅠ의 구성요소인 ‘B2M(Beta-2-microglobulin)’과 상호작용해 대식작용을 피할 수 있도록 도왔다. 연구팀은 이번 논문에서 대식세포의 식작용을 피하는 세 번째 면역관문분자로 CD24의 역할을 규명했다....

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