Tadepalli, Sirimuvva and Clements, Derek R. and Saravanan, Sanjana and Hornero, Rebeca Arroyo and Ludtke, Anja and Blackmore, Beau and Paulo, Joao A. and Gottfried-Blackmore, Andres and Seong, David and Park, Soyoon and Chan, Leslie and Kopecky, Benjamin J. and Liu, Zhaoyuan and Ginhoux, Florent and Lavine, Kory J. and Murphy, John Patrick and Mack, Matthias and Graves, Edward E. and Idoyaga, Juliana (2023) Rapid recruitment and IFN-I-mediated activation of monocytes dictate focal radiotherapy efficacy. SCIENCE IMMUNOLOGY, 8 (84): eadd7446. ISSN 2470-9468,
Full text not available from this repository. (Request a copy)Abstract
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 nonCRT 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | T-CELL RESPONSES; STEREOTACTIC BODY RADIOTHERAPY; DENDRITIC CELLS; CD8(+) T; CC-CHEMOKINE; NITRIC-OXIDE; NK CELLS; RADIATION; PROMOTES; CANCER; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Apr 2024 09:18 |
| Last Modified: | 09 Apr 2024 09:18 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60736 |
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