인문학
사회과학
자연과학
공학
의약학
농수해양학
예술체육학
복합학
DBpia AI
AI 에이전트
AI 아이디어
AI 리더
AI 뷰어
Citeasy
크롬 서지관리 다운로드
지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
초록·키워드
CD103<sup>+</sup> T cells mediate potent anti-tumor immune responses and correlate with favorable clinical outcomes in cancer patients. However, the mechanisms by which cancer cells influence the differentiation of these cells remain elusive. Herein, we demonstrate that cancer stem cells (CSCs) play a pivotal role in suppressing CD103<sup>+</sup> T cell differentiation in patients with non-small cell lung cancer (NSCLC). Specifically, CSCs facilitate the transfer of the metabolite acetyl-coenzyme A (acetyl-CoA) into interacting T cells via an exosome-dependent pathway. This process enhances the acetylation of B lymphocyte-induced maturation protein 1 (Blimp-1), a critical transcription factor governing CD103<sup>+</sup> T cell differentiation. Acetylation of Blimp-1 strengthens its interaction with the E3 ubiquitin ligase LIS1, thereby promoting Blimp-1 degradation, which ultimately blocks CD103<sup>+</sup> T cell differentiation. Accordingly, targeting CSCs and acetyl-CoA biosynthesis using CD133 antibody-conjugated nanoparticles increases tumor-infiltrating CD8<sup>+</sup>CD103<sup>+</sup> T cells and suppresses tumor growth. Importantly, studies using NSCLC patient-derived organoids (PDOs) and humanized PDO-NSG chimeras confirmed that blocking acetyl-CoA production, exosome secretion from CSCs, and key enzymes involved in Blimp-1 acetylation and ubiquitination effectively restores CD103<sup>+</sup> T cell differentiation. Altogether, CSC acetyl-CoA is a key contributor in impairing CD103<sup>+</sup> T cells through programming post-translational modifications, serving as a promising therapeutic target in anti-tumor therapy.
인공지능 문자 인식 모델을 통해 추출된 텍스트로, 일부 오타나 오류가 포함될 수 있으나 지속적으로 개선 중입니다.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
오류를 발견하셨다면 해당 부분을 드래그한 후 ' 를 통해 신고해주세요.
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