单核细胞
免疫系统
CD8型
癌症研究
效应器
肿瘤微环境
功能(生物学)
免疫学
放射治疗
免疫疗法
生物
细胞生物学
医学
内科学
作者
Sirimuvva Tadepalli,Derek R. Clements,Sanjana Saravanan,Rebeca Arroyo Hornero,Anja Lüdtke,Beau Blackmore,João A. Paulo,Andrés Gottfried-Blackmore,David Seong,Soyoon Park,Leslie Chan,Benjamin J. Kopecky,Zhaoyuan Liu,Florent Ginhoux,Kory J. Lavine,John P. Murphy,Matthias Mack,Edward E. Graves,Juliana Idoyaga
出处
期刊:Science immunology
[American Association for the Advancement of Science (AAAS)]
日期:2023-06-30
卷期号:8 (84)
被引量:4
标识
DOI:10.1126/sciimmunol.add7446
摘要
The recruitment of monocytes and their differentiation into immunosuppressive cells is associated with the low efficacy of preclinical nonconformal radiotherapy (RT) for tumors. However, nonconformal RT (non-CRT) does not mimic clinical practice, and little is known about the role of monocytes after RT modes used in patients, such as conformal RT (CRT). Here, we investigated the acute immune response induced by after CRT. Contrary to non-CRT approaches, we found that CRT induces a rapid and robust recruitment of monocytes to the tumor that minimally differentiate into tumor-associated macrophages or dendritic cells but instead up-regulate major histocompatibility complex II and costimulatory molecules. We found that these large numbers of infiltrating monocytes are responsible for activating effector polyfunctional CD8 + tumor-infiltrating lymphocytes that reduce tumor burden. Mechanistically, we show that monocyte-derived type I interferon is pivotal in promoting monocyte accumulation and immunostimulatory function in a positive feedback loop. We also demonstrate that monocyte accumulation in the tumor microenvironment is hindered when RT inadvertently affects healthy tissues, as occurs in non-CRT. Our results unravel the immunostimulatory function of monocytes during clinically relevant modes of RT and demonstrate that limiting the exposure of healthy tissues to radiation has a positive therapeutic effect on the overall antitumor immune response.
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