UCI研究により、概日時計を癌免疫療法の強化に活用できることが明らかに(UC Irvine study reveals circadian clock can be leveraged to enhance cancer immunotherapy)


2024-05-28 カリフォルニア大学校アーバイン校(UCI)

◆Nature Immunologyに発表されたこの研究は、サーカディアンリズム、免疫調節、腫瘍発生の関係を解明し、個人の体内時計に基づく時間最適化治療の新たな可能性を示しています。研究では、コロン癌モデルを用い、体内時計がT細胞の活性化を抑制するミエロイド細胞の数を制御することを発見しました。また、免疫療法をミエロイド細胞が最も多い時間帯に提供することで、治療効果が大幅に向上することを確認しました。


腫瘍免疫抑制の概日制御が免疫チェックポイント阻害薬の有効性に影響する Circadian control of tumor immunosuppression affects efficacy of immune checkpoint blockade

Bridget M. Fortin,Shannon M. Pfeiffer,Jacob Insua-Rodríguez,Hamad Alshetaiwi,Alexander Moshensky,Wei A. Song,Alisa L. Mahieu,Sung Kook Chun,Amber N. Lewis,Alex Hsu,Isam Adam,Oliver S. Eng,Nicholas R. Pannunzio,Marcus M. Seldin,Ivan Marazzi,Francesco Marangoni,Devon A. Lawson,Kai Kessenbrock & Selma Masri
Nature Immunology  Published:28 May 2024

extended data figure 1


The circadian clock is a critical regulator of immunity, and this circadian control of immune modulation has an essential function in host defense and tumor immunosurveillance. Here we use a single-cell RNA sequencing approach and a genetic model of colorectal cancer to identify clock-dependent changes to the immune landscape that control the abundance of immunosuppressive cells and consequent suppression of cytotoxic CD8+ T cells. Of these immunosuppressive cell types, PD-L1-expressing myeloid-derived suppressor cells (MDSCs) peak in abundance in a rhythmic manner. Disruption of the epithelial cell clock regulates the secretion of cytokines that promote heightened inflammation, recruitment of neutrophils and the subsequent development of MDSCs. We also show that time-of-day anti-PD-L1 delivery is most effective when synchronized with the abundance of immunosuppressive MDSCs. Collectively, these data indicate that circadian gating of tumor immunosuppression informs the timing and efficacy of immune checkpoint inhibitors.