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YTHDF2 inhibition potentiates radiotherapy antitumor efficacy

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YTHDF2 inhibition potentiates radiotherapy antitumor efficacy. / Wang, Liangliang; Dou, Xiaoyang; Chen, Shijie; Yu, Xianbin; Huang, Xiaona; Zhang, Linda; Chen, Yantao; Wang, Jiaai; Yang, Kaiting; Bugno, Jason; Pitroda, Sean; Ding, Xingchen; Piffko, Andras; Si, Wei; Chen, Chao; Jiang, Hualiang; Zhou, Bing; Chmura, Steven J; Luo, Cheng; Liang, Hua Laura; He, Chuan; Weichselbaum, Ralph R.

in: CANCER CELL, Jahrgang 41, Nr. 7, 10.07.2023, S. 1294-1308.e8.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Wang, L, Dou, X, Chen, S, Yu, X, Huang, X, Zhang, L, Chen, Y, Wang, J, Yang, K, Bugno, J, Pitroda, S, Ding, X, Piffko, A, Si, W, Chen, C, Jiang, H, Zhou, B, Chmura, SJ, Luo, C, Liang, HL, He, C & Weichselbaum, RR 2023, 'YTHDF2 inhibition potentiates radiotherapy antitumor efficacy', CANCER CELL, Jg. 41, Nr. 7, S. 1294-1308.e8. https://doi.org/10.1016/j.ccell.2023.04.019

APA

Wang, L., Dou, X., Chen, S., Yu, X., Huang, X., Zhang, L., Chen, Y., Wang, J., Yang, K., Bugno, J., Pitroda, S., Ding, X., Piffko, A., Si, W., Chen, C., Jiang, H., Zhou, B., Chmura, S. J., Luo, C., ... Weichselbaum, R. R. (2023). YTHDF2 inhibition potentiates radiotherapy antitumor efficacy. CANCER CELL, 41(7), 1294-1308.e8. https://doi.org/10.1016/j.ccell.2023.04.019

Vancouver

Wang L, Dou X, Chen S, Yu X, Huang X, Zhang L et al. YTHDF2 inhibition potentiates radiotherapy antitumor efficacy. CANCER CELL. 2023 Jul 10;41(7):1294-1308.e8. https://doi.org/10.1016/j.ccell.2023.04.019

Bibtex

@article{e08030b339e444c8a6ea1a6ff75af87e,
title = "YTHDF2 inhibition potentiates radiotherapy antitumor efficacy",
abstract = "RNA N6-methyladenosine (m6A) modification is implicated in cancer progression. However, the impact of m6A on the antitumor effects of radiotherapy and the related mechanisms are unknown. Here we show that ionizing radiation (IR) induces immunosuppressive myeloid-derived suppressor cell (MDSC) expansion and YTHDF2 expression in both murine models and humans. Following IR, loss of Ythdf2 in myeloid cells augments antitumor immunity and overcomes tumor radioresistance by altering MDSC differentiation and inhibiting MDSC infiltration and suppressive function. The remodeling of the landscape of MDSC populations by local IR is reversed by Ythdf2 deficiency. IR-induced YTHDF2 expression relies on NF-κB signaling; YTHDF2 in turn leads to NF-κB activation by directly binding and degrading transcripts encoding negative regulators of NF-κB signaling, resulting in an IR-YTHDF2-NF-κB circuit. Pharmacological inhibition of YTHDF2 overcomes MDSC-induced immunosuppression and improves combined IR and/or anti-PD-L1 treatment. Thus, YTHDF2 is a promising target to improve radiotherapy (RT) and RT/immunotherapy combinations.",
keywords = "Animals, Humans, Mice, Gene Expression Regulation, Myeloid Cells/metabolism, Neoplasms/genetics, NF-kappa B/metabolism, RNA-Binding Proteins/metabolism, Signal Transduction",
author = "Liangliang Wang and Xiaoyang Dou and Shijie Chen and Xianbin Yu and Xiaona Huang and Linda Zhang and Yantao Chen and Jiaai Wang and Kaiting Yang and Jason Bugno and Sean Pitroda and Xingchen Ding and Andras Piffko and Wei Si and Chao Chen and Hualiang Jiang and Bing Zhou and Chmura, {Steven J} and Cheng Luo and Liang, {Hua Laura} and Chuan He and Weichselbaum, {Ralph R}",
note = "Copyright {\textcopyright} 2023 Elsevier Inc. All rights reserved.",
year = "2023",
month = jul,
day = "10",
doi = "10.1016/j.ccell.2023.04.019",
language = "English",
volume = "41",
pages = "1294--1308.e8",
journal = "CANCER CELL",
issn = "1535-6108",
publisher = "Cell Press",
number = "7",

}

RIS

TY - JOUR

T1 - YTHDF2 inhibition potentiates radiotherapy antitumor efficacy

AU - Wang, Liangliang

AU - Dou, Xiaoyang

AU - Chen, Shijie

AU - Yu, Xianbin

AU - Huang, Xiaona

AU - Zhang, Linda

AU - Chen, Yantao

AU - Wang, Jiaai

AU - Yang, Kaiting

AU - Bugno, Jason

AU - Pitroda, Sean

AU - Ding, Xingchen

AU - Piffko, Andras

AU - Si, Wei

AU - Chen, Chao

AU - Jiang, Hualiang

AU - Zhou, Bing

AU - Chmura, Steven J

AU - Luo, Cheng

AU - Liang, Hua Laura

AU - He, Chuan

AU - Weichselbaum, Ralph R

N1 - Copyright © 2023 Elsevier Inc. All rights reserved.

PY - 2023/7/10

Y1 - 2023/7/10

N2 - RNA N6-methyladenosine (m6A) modification is implicated in cancer progression. However, the impact of m6A on the antitumor effects of radiotherapy and the related mechanisms are unknown. Here we show that ionizing radiation (IR) induces immunosuppressive myeloid-derived suppressor cell (MDSC) expansion and YTHDF2 expression in both murine models and humans. Following IR, loss of Ythdf2 in myeloid cells augments antitumor immunity and overcomes tumor radioresistance by altering MDSC differentiation and inhibiting MDSC infiltration and suppressive function. The remodeling of the landscape of MDSC populations by local IR is reversed by Ythdf2 deficiency. IR-induced YTHDF2 expression relies on NF-κB signaling; YTHDF2 in turn leads to NF-κB activation by directly binding and degrading transcripts encoding negative regulators of NF-κB signaling, resulting in an IR-YTHDF2-NF-κB circuit. Pharmacological inhibition of YTHDF2 overcomes MDSC-induced immunosuppression and improves combined IR and/or anti-PD-L1 treatment. Thus, YTHDF2 is a promising target to improve radiotherapy (RT) and RT/immunotherapy combinations.

AB - RNA N6-methyladenosine (m6A) modification is implicated in cancer progression. However, the impact of m6A on the antitumor effects of radiotherapy and the related mechanisms are unknown. Here we show that ionizing radiation (IR) induces immunosuppressive myeloid-derived suppressor cell (MDSC) expansion and YTHDF2 expression in both murine models and humans. Following IR, loss of Ythdf2 in myeloid cells augments antitumor immunity and overcomes tumor radioresistance by altering MDSC differentiation and inhibiting MDSC infiltration and suppressive function. The remodeling of the landscape of MDSC populations by local IR is reversed by Ythdf2 deficiency. IR-induced YTHDF2 expression relies on NF-κB signaling; YTHDF2 in turn leads to NF-κB activation by directly binding and degrading transcripts encoding negative regulators of NF-κB signaling, resulting in an IR-YTHDF2-NF-κB circuit. Pharmacological inhibition of YTHDF2 overcomes MDSC-induced immunosuppression and improves combined IR and/or anti-PD-L1 treatment. Thus, YTHDF2 is a promising target to improve radiotherapy (RT) and RT/immunotherapy combinations.

KW - Animals

KW - Humans

KW - Mice

KW - Gene Expression Regulation

KW - Myeloid Cells/metabolism

KW - Neoplasms/genetics

KW - NF-kappa B/metabolism

KW - RNA-Binding Proteins/metabolism

KW - Signal Transduction

U2 - 10.1016/j.ccell.2023.04.019

DO - 10.1016/j.ccell.2023.04.019

M3 - SCORING: Journal article

C2 - 37236197

VL - 41

SP - 1294-1308.e8

JO - CANCER CELL

JF - CANCER CELL

SN - 1535-6108

IS - 7

ER -