Control of tumor-associated macrophages and T cells in glioblastoma via AHR and CD39

Takenaka, Maisa C.; Gabriely, Galina; Rothhammer, Veit; Mascanfroni, Iván; Wheeler, Michael A.; Chao, Chun‐Cheih; Gutiérrez-Vázquez, Cristina; Kenison, Jessica E.; Tjon, Emily; Barroso, Andréia; Vandeventer, Tyler; Lima, Kalil Alves de; Rothweiler, Sonja; Mayo, Lior; Ghannam, Soufiene; Zandee, Stéphanie; Healy, Luke M.; Sherr, David H.; Farez, Mauricio; Prat, Alexandre; Antel, Jack P.; Reardon, David A.; Zhang, Hailei; Robson, Simon C.; Getz, Gad; Weiner, Howard L.; Quintana, Francisco J.

doi:10.1038/s41593-019-0370-y

Cited by 332 publications

(274 citation statements)

References 56 publications

Supporting

Mentioning

262

Contrasting

Order By: Relevance

“…While SETD7 probably drives the progression of gastric cancer, the modification of SETD7 would favour the tumour suppressor function of E2F1 in breast cancer . The important transcription factor KLF4, acted as a suppressor in metastasis and proliferation of cancer cells in colorectal cancer, while driven expression of KLF4 in tumour‐associated macrophages promoted immunosuppression to facilitate tumour growth in glioblastoma . However, by means of this study and our previous research, we demonstrated that SETD7 and KLF4 were two evident tumour suppressor genes in BCa.…”

Section: Discussionmentioning

confidence: 43%

METTL3/YTHDF2 m⁶A axis promotes tumorigenesis by degrading SETD7 and KLF4 mRNAs in bladder cancer

Xie

Ying

et al. 2020

J Cellular Molecular Medi

104

View full text Add to dashboard Cite

| INTRODUC TI ONBladder cancer (BCa) is the most common malignant tumour of the urinary tract and the 10th most common type of carcinoma worldwide. Approximately 549 000 new cases and 200 000 deaths were estimated by GLOBOCAN in 2018. 1 In 2019, approximately 80 470 patients (including 61 700 men) were diagnosed with BCa and 17 670 patients (including 12 870 men) died from BCa in the United States; thus, BCa ranks the forth in incidence and eighth in mortality in men. 2 The increasing trend in these numbers constantly urges researchers to better understand the mechanisms underlying the pathogenesis of BCa to identify potential therapies against BCa. m 6 A, a modification first identified in mRNA-enriched RNA fractions in 1974, 3 refers to methylation of the N6 position of adenosine bases, which are widely distributed in the mammalian mRNA. 4,5 With the application of available methods for detecting m 6 A, insights into the regulatory mechanism have been revealed in recent years. m 6 A RNA modification is a dynamic and reversible posttranscriptional modification process maintained by a multicomponent Abstract N6-Methyladenosine (m 6 A) modification, the most prevalent modification of eukaryotic messenger RNA (mRNA), is involved in the progression of various tumours.However, the specific role of m 6 A in bladder cancer (BCa) is still poorly understood.In this study, we demonstrated the tumour-promoting function and specific regulatory mechanism of m 6 A axis, consisting of the core 'writer' protein METTL3 and the major reader protein YTHDF2. Depletion of METTL3 impaired cancer proliferation and cancer metastasis in vitro and in vivo. Through transcriptome sequencing, m 6 A methylated RNA immunoprecipitation (MeRIP) and RIP, we determined that the METTL3/YTHDF2 m 6 A axis directly degraded the mRNAs of the tumour suppressors SETD7 and KLF4, contributing to the progression of BCa. In addition, overexpression of SETD7 and KLF4 revealed a phenotype consistent with that induced by depletion of the m 6 A axis. Thus, our findings on the METTL3/YTHDF2/SETD7/KLF4 m 6 A axis provide the insight into the underlying mechanism of carcinogenesis and highlight potential therapeutic targets for BCa. K E Y W O R D Sbladder cancer, carcinogenesis, METTL3/YTHDF2 m 6 A axis, mRNA degradation, RNA modification | 4093 XIE Et al.

show abstract

Section: Discussionmentioning

confidence: 43%

METTL3/YTHDF2 m⁶A axis promotes tumorigenesis by degrading SETD7 and KLF4 mRNAs in bladder cancer

Xie

Ying

et al. 2020

J Cellular Molecular Medi

104

View full text Add to dashboard Cite

show abstract

“…As previously described, the ectonucleotidases CD39 and CD73 hydrolyze ATP or ADP into AMP and further yield adenosine in a highly coordinated enzymatic process [88,89]. CD39 and CD73 are expressed by cancer cells and different immune cell populations and are responsible for the regulation of the balance between proinflammatory ATP and immunosuppressive adenosine in the tumor microenvironment [48,49,90,91]. Li et al demonstrated that CD39 and CD73 were expressed on MDSCs in the peripheral blood of patients with NSCLC and that CD39 + CD73 + MDSCs had an immunosuppressive function.…”

Section: Mdscs Are Associated With Chemotherapy Resistancementioning

confidence: 98%

Myeloid-derived suppressor cells—new and exciting players in lung cancer

et al. 2020

View full text Add to dashboard Cite

Lung cancer (LC) is the leading cause of cancer-related death worldwide due to its late diagnosis and poor outcomes. As has been found for other types of tumors, there is increasing evidence that myeloid-derived suppressor cells (MDSCs) play important roles in the promotion and progression of LC. Here, we briefly introduce the definition of MDSCs and their immunosuppressive functions. We next specifically discuss the multiple roles of MDSCs in the lung tumor microenvironment, including those in tumor growth and progression mediated by inhibiting antitumor immunity, and the associations of MDSCs with a poor prognosis and increased resistance to chemotherapy and immunotherapy. Finally, we also discuss preclinical and clinical treatment strategies targeting MDSCs, which may have the potential to enhance the efficacy of immunotherapy.

show abstract

“…This approach has identified excess glutamate secretion through the glial xCT antiporter (13), along with synaptic disinhibition due to cell death, loss of KCC2 chloride gradients, and degradation of perineuronal nets (PNNs) that protect vulnerable fast-spiking interneurons (14,15) as important mechanisms contributing to epileptogenesis. However, tumor-specific immunity plays a critical role in the GBM microenvironment and even alters therapeutic response biology (16). In SCID mice, although the tumor cell lines studied are patient-derived, cultured xenografts may lack specific malignant cellular subsets and interactions that arise in a developing host brain, and their proliferation in an immunocompromised adult cortex may or may not fully recapitulate the complex evolution of tumor cell-host neuron interactions in the peritumoral microenvironment.…”

Section: Pathogenesis Of Peritumoral Hyperexcitability In An Immunocomentioning

confidence: 99%

Pathogenesis of peritumoral hyperexcitability in an immunocompetent CRISPR-based glioblastoma model

Hatcher¹,

Yu²,

Meyer³

et al. 2020

Journal of Clinical Investigation

View full text Add to dashboard Cite

Control of tumor-associated macrophages and T cells in glioblastoma via AHR and CD39

Cited by 332 publications

References 56 publications

METTL3/YTHDF2 m⁶A axis promotes tumorigenesis by degrading SETD7 and KLF4 mRNAs in bladder cancer

METTL3/YTHDF2 m⁶A axis promotes tumorigenesis by degrading SETD7 and KLF4 mRNAs in bladder cancer

Myeloid-derived suppressor cells—new and exciting players in lung cancer

Pathogenesis of peritumoral hyperexcitability in an immunocompetent CRISPR-based glioblastoma model

Contact Info

Product

Resources

About

Control of tumor-associated macrophages and T cells in glioblastoma via AHR and CD39

Cited by 332 publications

References 56 publications

METTL3/YTHDF2 m6A axis promotes tumorigenesis by degrading SETD7 and KLF4 mRNAs in bladder cancer

METTL3/YTHDF2 m6A axis promotes tumorigenesis by degrading SETD7 and KLF4 mRNAs in bladder cancer

Myeloid-derived suppressor cells—new and exciting players in lung cancer

Pathogenesis of peritumoral hyperexcitability in an immunocompetent CRISPR-based glioblastoma model

Contact Info

Product

Resources

About

METTL3/YTHDF2 m⁶A axis promotes tumorigenesis by degrading SETD7 and KLF4 mRNAs in bladder cancer

METTL3/YTHDF2 m⁶A axis promotes tumorigenesis by degrading SETD7 and KLF4 mRNAs in bladder cancer