医学
封锁
启动(农业)
淋巴瘤
CD8型
癌症研究
抗原
免疫学
内科学
生物
植物
发芽
受体
作者
Linda Hammerich,Thomas U. Marron,Ranjan Upadhyay,Judit Svensson‐Arvelund,Maxime Dhainaut,Shafinaz Hussein,Yougen Zhan,Dana Ostrowski,Michael Yellin,Henry C. Marsh,Andrés M. Salazar,Adeeb Rahman,Brian D. Brown,Miriam Mérad,Joshua Brody
出处
期刊:Nature Medicine
[Springer Nature]
日期:2019-04-08
卷期号:25 (5): 814-824
被引量:333
标识
DOI:10.1038/s41591-019-0410-x
摘要
Indolent non-Hodgkin’s lymphomas (iNHLs) are incurable with standard therapy and are poorly responsive to checkpoint blockade. Although lymphoma cells are efficiently killed by primed T cells, in vivo priming of anti-lymphoma T cells has been elusive. Here, we demonstrate that lymphoma cells can directly prime T cells, but in vivo immunity still requires cross-presentation. To address this, we developed an in situ vaccine (ISV), combining Flt3L, radiotherapy, and a TLR3 agonist, which recruited, antigen-loaded and activated intratumoral, cross-presenting dendritic cells (DCs). ISV induced anti-tumor CD8+ T cell responses and systemic (abscopal) cancer remission in patients with advanced stage iNHL in an ongoing trial (
NCT01976585
). Non-responding patients developed a population of PD1+CD8+ T cells after ISV, and murine tumors became newly responsive to PD1 blockade, prompting a follow-up trial of the combined therapy. Our data substantiate that recruiting and activating intratumoral, cross-priming DCs is achievable and critical to anti-tumor T cell responses and PD1-blockade efficacy. In situ vaccine recruits and activates cross-presenting dendritic cells and augments PD1 blockade efficacy in patients with indolent non-Hodgkin’s lymphoma.
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