YTHDF2 upregulation and relocation dictate CD8 T cell polyfunctionality in tumor immunity DOI
Haiyan Zhang, Xiao-Jing Luo,

Wei Yang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 16, 2024

Abstract Epigenetic traits impact the antitumor function of CD8 T cells, yet whether and how RNA methylation programs engage in cell immunity is poorly understood. Here we show that N 6 -methyladenosine (m A) reader YTHDF2 highly expressed early effector or effector-like cells partially distributed nucleus. loss exacerbates tumor progression confers unresponsiveness to PD-1 blockade mice humans. In addition initiating decay for mitochondrial fitness, can orchestrate chromatin regulation promote polyfunctionality. YTHDF2-mediatd preservation gene transcription arises from interaction with IKZF1/3. Accordingly, immunotherapy-induced efficacy could be largely restored YTHDF2-deficient through combinational use lenalidomide. Moreover, m A recognition fundamental translocation nucleus autoregulation at level. Thus, coordinates epitranscriptional transcriptional networks potentiate immunity. Highlights expression distribution underpin threshold bona fide response Canonical YTHDF2-mRNA pathway alleviates stress exhaustion Nuclear sequesters IKZF1/3-mediated repression safeguard polyfunctionality The tumoricidal activity repaired synergy anti-PD-1 lenalidomide

Language: Английский

The role of RNA methylation in tumor immunity and its potential in immunotherapy DOI Creative Commons
Yan Li,

Haoer Jin,

Qingling Li

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: June 20, 2024

Abstract RNA methylation, a prevalent post-transcriptional modification, has garnered considerable attention in research circles. It exerts regulatory control over diverse biological functions by modulating splicing, translation, transport, and stability. Notably, studies have illuminated the substantial impact of methylation on tumor immunity. The primary types encompass N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), 3-methylcytidine (m3C). Compelling evidence underscores involvement regulating microenvironment (TME). By affecting translation stability through "writers", "erasers" "readers", influence dysregulation immune cells factors. Consequently, plays pivotal role immunity mediating various behaviors, encompassing proliferation, invasion, metastasis, etc. In this review, we discussed mechanisms several methylations, providing comprehensive overview their roles underlying within among immunocytes. exploring how these modifications mediate evasion, also examine potential applications immunotherapy. This review aims to provide novel insights strategies for identifying targets advancing cancer immunotherapy efficacy.

Language: Английский

Citations

32
Radiotherapy, immunity, and immune checkpoint inhibitors DOI
Connor Lynch, Sean P. Pitroda, Ralph R. Weichselbaum

et al.

The Lancet Oncology, Journal Year: 2024, Volume and Issue: 25(8), P. e352 - e362

Published: July 29, 2024

Language: Английский

Citations

25
YTHDF2/m6A/NF‐κB axis controls anti‐tumor immunity by regulating intratumoral Tregs DOI
Linda Zhang, Xiaoyang Dou, Zhong Zheng

et al.

The EMBO Journal, Journal Year: 2023, Volume and Issue: 42(15)

Published: June 22, 2023

Language: Английский

Citations

29
The YTHDF proteins display distinct cellular functions on m6A-modified RNA DOI
Zhongyu Zou, Chuan He

Trends in Biochemical Sciences, Journal Year: 2024, Volume and Issue: 49(7), P. 611 - 621

Published: April 26, 2024

Language: Английский

Citations

13
RNA modifications in cancer DOI Creative Commons

Han Wu,

Shi Chen, Xiang Li

et al.

MedComm, Journal Year: 2025, Volume and Issue: 6(1)

Published: Jan. 1, 2025

Abstract RNA modifications are emerging as critical cancer regulators that influence tumorigenesis and progression. Key modifications, such N6‐methyladenosine (m 6 A) 5‐methylcytosine 5 C), implicated in various cellular processes. These regulated by proteins write, erase, read modulate stability, splicing, translation, degradation. Recent studies have highlighted their roles metabolic reprogramming, signaling pathways, cell cycle control, which essential for tumor proliferation survival. Despite these scientific advances, the precise mechanisms affect remain inadequately understood. This review comprehensively examines role play proliferation, metastasis, programmed death, including apoptosis, autophagy, ferroptosis. It explores effects on epithelial–mesenchymal transition (EMT) immune microenvironment, particularly metastasis. Furthermore, modifications’ potential therapies, conventional treatments, immunotherapy, targeted is discussed. By addressing aspects, this aims to bridge current research gaps underscore therapeutic of targeting improve treatment strategies patient outcomes.

Language: Английский

Citations

1
Drug resistance and tumor immune microenvironment: An overview of current understandings (Review) DOI Creative Commons
Yan Liu, Jun Liang, Yanping Zhang

et al.

International Journal of Oncology, Journal Year: 2024, Volume and Issue: 65(4)

Published: Aug. 30, 2024

The use of antitumor drugs represents a reliable strategy for cancer therapy. Unfortunately, drug resistance has become increasingly common and contributes to tumor metastasis local recurrence. immune microenvironment (TME) consists cells, cytokines immunomodulators, collectively they influence the response treatment. Epigenetic changes including DNA methylation histone modification, as well increased exportation have been reported contribute development in cancers. In past few years, majority studies on tumors only focused progression from mechanistic standpoint; examined whether TME can also affect growth resistance. Recently, emerging evidence raised more concerns regarding role present review, it was discussed how suppressive adapts characterized by cooperation cytokines, stromal cells extracellular matrix. Furthermore, reviewed these immunological or metabolic alter immuno‑surveillance thus facilitate addition, potential targets developing novel therapeutic strategies improve individualized therapy treatment were revealed.

Language: Английский

Citations

8
YTHDF2 promotes ATP synthesis and immune evasion in B cell malignancies DOI
Zhenhua Chen, Chengwu Zeng, Lu Yang

et al.

Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

Citations

7
The m6A methyltransferase METTL3 modifies Kcnk6 promoting on inflammation associated carcinogenesis is essential for colon homeostasis and defense system through histone lactylation dependent YTHDF2 binding DOI
Xiaolong Yuan, Qiong Wang, Jun Zhao

et al.

International Reviews of Immunology, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 16

Published: Sept. 13, 2024

Inflammation induces tumor formation and plays a crucial role in progression prognosis. KCNK6, by regulating K(+) efflux to reduce NLRP3 Inflammasome-induced lung injury, relaxes the aorta. This study aims elucidate effects biological mechanism of KCNK6 inflammation-associated carcinogenesis, which may be essential for colon homeostasis defense system. To induce colitis, mice were given 3.0% Dextran Sodium Sulfate (DSS) their drinking water 7 days. The Azoxymethane (AOM) +DSS method was used cancer model. Bone marrow-derived macrophages (BMDM) from Kcnk6-/- mice, AW264.7 cells, human HCT116 Caco2 cells as

Language: Английский

Citations

6
YTHDF2 upregulation and subcellular localization dictate CD8 T cell polyfunctionality in anti-tumor immunity DOI Creative Commons
Haiyan Zhang, Xiao-Jing Luo,

Wei Yang

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Nov. 5, 2024

RNA methylation is an important regulatory process to determine immune cell function but how it affects the anti-tumor activity of CD8 T cells not fully understood. Here we show that N6-methyladenosine (m6A) reader YTHDF2 highly expressed in early effector or effector-like cells. We find facilitates nascent synthesis, and m6A recognition fundamental for this distinctively nuclear protein, which also reinforces its autoregulation at level. Loss exacerbates tumor progression confers unresponsiveness PD-1 blockade mice humans. In addition initiating decay necessary mitochondrial fitness, orchestrates chromatin changes promote polyfunctionality. interacts with IKZF1/3, sustained transcription their target genes. Accordingly, immunotherapy-induced efficacy could be largely restored YTHDF2-deficient through combinational use IKZF1/3 inhibitor lenalidomide a mouse model. Thus, coordinates epi-transcriptional transcriptional networks potentiate immunity, inform therapeutic intervention. has recently identified as mechanism governing functional cellular states, effect on antitumour + explored. authors assign essential nuclear, m6A-recognition-dependent YTHDF2, which, conjunction role IKZF1/3-mediated gene transcription, governs

Language: Английский

Citations

5
ADAMDEC1 promotes the malignant progression of cholangiocarcinoma by regulating NF-κB signaling pathway DOI Creative Commons
Shuo Zhou, Yuhang Yang,

Feiyu Qi

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 4, 2025

Cholangiocarcinoma (CCA), a highly aggressive form of cancer, is known for its high mortality rate. A Disintegrin and Metalloprotease Domain-like Protein Decysin-1 (ADAMDEC1) can promote the development metastasis in various tumors by degrading extracellular matrix. However, regulatory mechanism CCA remains unclear. Public databases clinical tissue samples were used to evaluate whether ADAMDEC1 expression was correlated with prognosis CCA. We investigated ADAMDEC1-related genes proteins assessed biological behaviors cells vitro through functional experiments. Meanwhile, interacting involvement nuclear factor-kappa B (NF-κB) signaling pathway screened verified bioinformatics analysis. The tumorigenicity also xenograft nude mouse model. Our results showed that expressed tumor tissues from patients positively poor prognosis. Interference cell lines targeting successfully constructed. Knockdown or MMP12 both affected cells, silencing inhibited growth vivo. Moreover, interacted MMP12, modulating promoting activation NF-κB pathway. study uncovered patterns roles tissues, highlighting connection Therefore, may serve as potential therapeutic target

Language: Английский

Citations

0