Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Typ-2-Diabetes und Adipositas Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Häufige urologisch-sexualmedizinische Themen in der Praxis sind das Thema des MMW-Webinars am 5. Juni von 17.30 bis 19 Uhr. Konkret geht es um die Frage, wann bei Harnwegsinfektionen auf Antibiotika verzichtet werden kann, und um ein Update zur Therapie von Libido- und Potenzstörungen des Mannes. Der dritte Vortrag behandelt sexuell übertragbare Krankheiten. Stellen Sie Ihre Fragen an die Experten und sammeln Sie 2 CME-Punkte. Jetzt gleich anmelden!
Erweiterte Suche
Anmelden
nach oben
Medical Oncology
Erschienen in: Medical Oncology 6/2024

01.06.2024 | Review Article

Role of m6A modifications in immune evasion and immunotherapy

verfasst von: Chunyu Wu, Lvyuan Li, Qiling Tang, Qianjin Liao, Pan Chen, Can Guo, Zhaoyang Zeng, Wei Xiong

Erschienen in: Medical Oncology | Ausgabe 6/2024

Einloggen, um Zugang zu erhalten

Abstract

RNA modification has garnered increasing attention in recent years due to its pivotal role in tumorigenesis and immune surveillance. N6-methyladenosine (m6A) modification is the most prevalent RNA modification, which can affect the expression of RNA by methylating adenylate at the sixth N position to regulate the occurrence and development of tumors. Dysregulation of m6A affects the activation of cancer-promoting pathways, destroys immune cell function, maintains immunosuppressive microenvironment, and promotes tumor cell growth. In this review, we delve into the latest insights into how abnormalities in m6A modification in both tumor and immune cells orchestrate immune evasion through the activation of signaling pathways. Furthermore, we explore how dysregulated m6A modification in tumor cells influences immune cells, thereby regulating tumor immune evasion via interactions within the tumor microenvironment (TME). Lastly, we highlight recent discoveries regarding specific inhibitors of m6A modulators and the encapsulation of m6A-targeting nanomaterials for cancer therapy, discussing their potential applications in immunotherapy.
Literatur
1.
2.
3.
4.
Xiao S, Cao S, Huang Q, Xia L, Deng M, Yang M, et al. The RNA N(6)-methyladenosine modification landscape of human fetal tissues. Nat Cell Biol. 2019;21(5):651–61.PubMedCrossRef
5.
Zhao W, Qi X, Liu L, Ma S, Liu J, Wu J. Epigenetic regulation of m(6)A modifications in human cancer. Mol Ther Nucleic Acids. 2020;19:405–12.PubMedCrossRef
6.
Oerum S, Meynier V, Catala M, Tisné C. A comprehensive review of m6A/m6Am RNA methyltransferase structures. Nucleic Acids Res. 2021;49(13):7239–55.PubMedPubMedCentralCrossRef
7.
Deng LJ, Deng WQ, Fan SR, Chen MF, Qi M, Lyu WY, et al. m6A modification: recent advances, anticancer targeted drug discovery and beyond. Mol Cancer. 2022;21(1):52.PubMedPubMedCentralCrossRef
8.
Shi H, Wei J, He C. Where, when, and how: context-dependent functions of RNA methylation writers, readers, and erasers. Mol Cell. 2019;74(4):640–50.PubMedPubMedCentralCrossRef
9.
Wojtas MN, Pandey RR, Mendel M, Homolka D, Sachidanandam R, Pillai RS. Regulation of m(6)A transcripts by the 3’→5’ RNA helicase YTHDC2 is essential for a successful meiotic program in the mammalian germline. Mol Cell. 2017;68(2):374-87.e12.PubMedCrossRef
10.
Xiao W, Adhikari S, Dahal U, Chen YS, Hao YJ, Sun BF, et al. Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing. Mol Cell. 2016;61(4):507–19.PubMedCrossRef
11.
Gu Y, Wu X, Zhang J, Fang Y, Pan Y, Shu Y, et al. The evolving landscape of N(6)-methyladenosine modification in the tumor microenvironment. Mol Ther. 2021;29(5):1703–15.PubMedPubMedCentralCrossRef
12.
van den Homberg DAL, van der Kwast R, Quax PHA, Nossent AY. N-6-Methyladenosine in Vasoactive microRNAs during Hypoxia; A Novel Role for METTL4. Int J Mol Sci. 2022;23(3).
13.
Gasparri ML, Besharat ZM, Farooqi AA, Khalid S, Taghavi K, Besharat RA, et al. MiRNAs and their interplay with PI3K/AKT/mTOR pathway in ovarian cancer cells: a potential role in platinum resistance. J Cancer Res Clin Oncol. 2018;144(12):2313–8.PubMedCrossRef
14.
Kim GW, Imam H, Khan M, Mir SA, Kim SJ, Yoon SK, et al. HBV-induced increased N6 methyladenosine modification of PTEN RNA affects innate immunity and contributes to HCC. Hepatology. 2021;73(2):533–47.PubMedCrossRef
15.
Jin S, Li M, Chang H, Wang R, Zhang Z, Zhang J, et al. The m6A demethylase ALKBH5 promotes tumor progression by inhibiting RIG-I expression and interferon alpha production through the IKKε/TBK1/IRF3 pathway in head and neck squamous cell carcinoma. Mol Cancer. 2022;21(1):97.PubMedPubMedCentralCrossRef
16.
Esteva FJ, Hubbard-Lucey VM, Tang J, Pusztai L. Immunotherapy and targeted therapy combinations in metastatic breast cancer. Lancet Oncol. 2019;20(3):e175–86.PubMedCrossRef
17.
18.
Kuang Z, Liu X, Zhang N, Dong J, Sun C, Yin M, et al. USP2 promotes tumor immune evasion via deubiquitination and stabilization of PD-L1. Cell Death Differ. 2023;30(10):2249–64.PubMedCrossRef
19.
Zhao Y, Huang S, Tan X, Long L, He Q, Liang X, et al. N(6) -methyladenosine-modified CBX1 regulates nasopharyngeal carcinoma progression through heterochromatin formation and STAT1 activation. Adv Sci (Weinh). 2022;9(36):e2205091.PubMedCrossRef
20.
Zhang L, Hou C, Chen C, Guo Y, Yuan W, Yin D, et al. The role of N(6)-methyladenosine (m(6)A) modification in the regulation of circRNAs. Mol Cancer. 2020;19(1):105.PubMedPubMedCentralCrossRef
21.
Liu Z, Wang T, She Y, Wu K, Gu S, Li L, et al. N(6)-methyladenosine-modified circIGF2BP3 inhibits CD8(+) T-cell responses to facilitate tumor immune evasion by promoting the deubiquitination of PD-L1 in non-small cell lung cancer. Mol Cancer. 2021;20(1):105.PubMedPubMedCentralCrossRef
22.
Ni Z, Sun P, Zheng J, Wu M, Yang C, Cheng M, et al. JNK signaling promotes bladder cancer immune escape by regulating METTL3-mediated m6A modification of PD-L1 mRNA. Cancer Res. 2022;82(9):1789–802.PubMedCrossRef
23.
Wan W, Ao X, Chen Q, Yu Y, Ao L, Xing W, et al. METTL3/IGF2BP3 axis inhibits tumor immune surveillance by upregulating N(6)-methyladenosine modification of PD-L1 mRNA in breast cancer. Mol Cancer. 2022;21(1):60.PubMedPubMedCentralCrossRef
24.
Wen J, Xue L, Wei Y, Liang J, Jia W, Yong T, et al. YTHDF2 is a therapeutic target for HCC by suppressing immune evasion and angiogenesis through ETV5/PD-L1/VEGFA axis. Adv Sci (Weinh). 2024:e2307242.
25.
Liu Y, Liang G, Xu H, Dong W, Dong Z, Qiu Z, et al. Tumors exploit FTO-mediated regulation of glycolytic metabolism to evade immune surveillance. Cell Metab. 2021;33(6):1221-33.e11.PubMedCrossRef
26.
Shimasaki N, Jain A, Campana D. NK cells for cancer immunotherapy. Nat Rev Drug Discov. 2020;19(3):200–18.PubMedCrossRef
27.
Gong Y, Klein Wolterink RGJ, Wang J, Bos GMJ, Germeraad WTV. Chimeric antigen receptor natural killer (CAR-NK) cell design and engineering for cancer therapy. J Hematol Oncol. 2021;14(1):73.PubMedPubMedCentralCrossRef
28.
Yuan F, Cai X, Cong Z, Wang Y, Geng Y, Aili Y, et al. Roles of the m(6)A modification of RNA in the glioblastoma microenvironment as revealed by single-cell analyses. Front Immunol. 2022;13:798583.PubMedPubMedCentralCrossRef
29.
30.
Becknell B, Caligiuri MA. Interleukin-2, interleukin-15, and their roles in human natural killer cells. Adv Immunol. 2005;86:209–39.PubMedCrossRef
31.
Carson WE, Fehniger TA, Haldar S, Eckhert K, Lindemann MJ, Lai CF, et al. A potential role for interleukin-15 in the regulation of human natural killer cell survival. J Clin Invest. 1997;99(5):937–43.PubMedPubMedCentralCrossRef
32.
Carson WE, Giri JG, Lindemann MJ, Linett ML, Ahdieh M, Paxton R, et al. Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor. J Exp Med. 1994;180(4):1395–403.PubMedCrossRef
33.
Song H, Song J, Cheng M, Zheng M, Wang T, Tian S, et al. METTL3-mediated m(6)A RNA methylation promotes the anti-tumour immunity of natural killer cells. Nat Commun. 2021;12(1):5522.PubMedPubMedCentralCrossRef
34.
Ma S, Yan J, Barr T, Zhang J, Chen Z, Wang LS, et al. The RNA m6A reader YTHDF2 controls NK cell antitumor and antiviral immunity. J Exp Med. 2021;218(8).
35.
Liu XS, Zhou LM, Yuan LL, Gao Y, Kui XY, Liu XY, et al. NPM1 is a prognostic biomarker involved in immune infiltration of lung adenocarcinoma and associated with m6A modification and glycolysis. Front Immunol. 2021;12:724741.PubMedPubMedCentralCrossRef
36.
37.
Han D, Liu J, Chen C, Dong L, Liu Y, Chang R, et al. Anti-tumour immunity controlled through mRNA m(6)A methylation and YTHDF1 in dendritic cells. Nature. 2019;566(7743):270–4.PubMedPubMedCentralCrossRef
38.
Wang H, Hu X, Huang M, Liu J, Gu Y, Ma L, et al. Mettl3-mediated mRNA m(6)A methylation promotes dendritic cell activation. Nat Commun. 2019;10(1):1898.PubMedPubMedCentralCrossRef
39.
Zhang F, Liu H, Duan M, Wang G, Zhang Z, Wang Y, et al. Crosstalk among m(6)A RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application. J Hematol Oncol. 2022;15(1):84.PubMedPubMedCentralCrossRef
40.
Park SL, Gebhardt T, Mackay LK. Tissue-resident memory T cells in cancer immunosurveillance. Trends Immunol. 2019;40(8):735–47.PubMedCrossRef
41.
Germain RN. T-cell development and the CD4-CD8 lineage decision. Nat Rev Immunol. 2002;2(5):309–22.PubMedCrossRef
42.
Li HB, Tong J, Zhu S, Batista PJ, Duffy EE, Zhao J, et al. m(6)A mRNA methylation controls T cell homeostasis by targeting the IL-7/STAT5/SOCS pathways. Nature. 2017;548(7667):338–42.PubMedPubMedCentralCrossRef
43.
Tong J, Cao G, Zhang T, Sefik E, Amezcua Vesely MC, Broughton JP, et al. m(6)A mRNA methylation sustains Treg suppressive functions. Cell Res. 2018;28(2):253–6.PubMedPubMedCentralCrossRef
44.
Li Y, Zheng JN, Wang EH, Gong CJ, Lan KF, Ding X. The m6A reader protein YTHDC2 is a potential biomarker and associated with immune infiltration in head and neck squamous cell carcinoma. PeerJ. 2020;8:e10385.PubMedPubMedCentralCrossRef
45.
Lu L, Zheng D, Qu J, Zhuang Y, Peng J, Lan S, et al. METTL16 predicts a favorable outcome and primes antitumor immunity in pancreatic ductal adenocarcinoma. Front Cell Dev Biol. 2022;10:759020.PubMedPubMedCentralCrossRef
46.
Ding C, Xu H, Yu Z, Roulis M, Qu R, Zhou J, et al. RNA m(6)A demethylase ALKBH5 regulates the development of γδ T cells. Proc Natl Acad Sci USA. 2022;119(33):e2203318119.PubMedPubMedCentralCrossRef
47.
Qin S, Liu G, Jin H, Chen X, He J, Xiao J, et al. The comprehensive expression and functional analysis of m6A modification “readers” in hepatocellular carcinoma. Aging (Albany NY). 2022;14(15):6269–98.PubMedCrossRef
48.
Na YR, Je S, Seok SH. Metabolic features of macrophages in inflammatory diseases and cancer. Cancer Lett. 2018;413:46–58.PubMedCrossRef
49.
Tong J, Wang X, Liu Y, Ren X, Wang A, Chen Z, et al. Pooled CRISPR screening identifies m(6)A as a positive regulator of macrophage activation. Sci Adv. 2021;7(18).
50.
Cai L, Li D, Feng Z, Gu X, Xu Q, Li Q. YTHDF2 regulates macrophage polarization through NF-κB and MAPK signaling pathway inhibition or p53 degradation. Dis Markers. 2022;2022:3153362.PubMedPubMedCentralCrossRef
51.
Wang X, Ji Y, Feng P, Liu R, Li G, Zheng J, et al. The m6A reader IGF2BP2 regulates macrophage phenotypic activation and inflammatory diseases by stabilizing TSC1 and PPARγ. Adv Sci (Weinh). 2021;8(13):2100209.PubMedCrossRef
52.
Dong L, Chen C, Zhang Y, Guo P, Wang Z, Li J, et al. The loss of RNA N(6)-adenosine methyltransferase Mettl14 in tumor-associated macrophages promotes CD8(+) T cell dysfunction and tumor growth. Cancer Cell. 2021;39(7):945-57.e10.PubMedCrossRef
53.
Ma S, Sun B, Duan S, Han J, Barr T, Zhang J, et al. YTHDF2 orchestrates tumor-associated macrophage reprogramming and controls antitumor immunity through CD8(+) T cells. Nat Immunol. 2023.
54.
Yin H, Zhang X, Yang P, Zhang X, Peng Y, Li D, et al. RNA m6A methylation orchestrates cancer growth and metastasis via macrophage reprogramming. Nat Commun. 2021;12(1):1394.PubMedPubMedCentralCrossRef
55.
Liu Y, Shi M, He X, Cao Y, Liu P, Li F, et al. LncRNA-PACERR induces pro-tumour macrophages via interacting with miR-671-3p and m6A-reader IGF2BP2 in pancreatic ductal adenocarcinoma. J Hematol Oncol. 2022;15(1):52.PubMedPubMedCentralCrossRef
56.
Gong PJ, Shao YC, Yang Y, Song WJ, He X, Zeng YF, et al. Analysis of N6-methyladenosine methyltransferase reveals METTL14 and ZC3H13 as tumor suppressor genes in breast cancer. Front Oncol. 2020;10:578963.PubMedPubMedCentralCrossRef
57.
Siemińska I, Poljańska E, Baran J. Granulocytes and cells of granulocyte origin-the relevant players in colorectal cancer. Int J Mol Sci. 2021;22(7).
58.
Su G, Liu T, Han X, Sun H, Che W, Hu K, et al. YTHDF2 is a potential biomarker and associated with immune infiltration in kidney renal clear cell carcinoma. Front Pharmacol. 2021;12:709548.PubMedPubMedCentralCrossRef
59.
Yi L, Wu G, Guo L, Zou X, Huang P. Comprehensive analysis of the PD-L1 and immune infiltrates of m(6)A RNA methylation regulators in head and neck squamous cell carcinoma. Mol Ther Nucleic Acids. 2020;21:299–314.PubMedPubMedCentralCrossRef
60.
Xiong J, He J, Zhu J, Pan J, Liao W, Ye H, et al. Lactylation-driven METTL3-mediated RNA m(6)A modification promotes immunosuppression of tumor-infiltrating myeloid cells. Mol Cell. 2022;82(9):1660-77.e10.PubMedCrossRef
61.
Wang L, Dou X, Chen S, Yu X, Huang X, Zhang L, et al. YTHDF2 inhibition potentiates radiotherapy antitumor efficacy. Cancer Cell. 2023.
62.
Bejarano L, Jordāo MJC, Joyce JA. Therapeutic targeting of the tumor microenvironment. Cancer Discov. 2021;11(4):933–59.PubMedCrossRef
63.
Zhang F, Guo J, Zhang Z, Qian Y, Wang G, Duan M, et al. Mesenchymal stem cell-derived exosome: a tumor regulator and carrier for targeted tumor therapy. Cancer Lett. 2022;526:29–40.PubMedCrossRef
64.
Chen H, Pan Y, Zhou Q, Liang C, Wong CC, Zhou Y, et al. METTL3 inhibits antitumor immunity by targeting m(6)A-BHLHE41-CXCL1/CXCR2 axis to promote colorectal cancer. Gastroenterology. 2022;163(4):891–907.PubMedCrossRef
65.
He J, Zhou M, Yin J, Wan J, Chu J, Jia J, et al. METTL3 restrains papillary thyroid cancer progression via m(6)A/c-Rel/IL-8-mediated neutrophil infiltration. Mol Ther. 2021;29(5):1821–37.PubMedPubMedCentralCrossRef
66.
Zeng X, Chen K, Li L, Tian J, Ruan W, Hu Z, et al. Epigenetic activation of RBM15 promotes clear cell renal cell carcinoma growth, metastasis and macrophage infiltration by regulating the m6A modification of CXCL11. Free Radic Biol Med. 2022;184:135–47.PubMedCrossRef
67.
Dong F, Qin X, Wang B, Li Q, Hu J, Cheng X, et al. ALKBH5 facilitates hypoxia-induced paraspeckle assembly and IL8 secretion to generate an immunosuppressive tumor microenvironment. Cancer Res. 2021;81(23):5876–88.PubMedCrossRef
68.
You Y, Wen D, Zeng L, Lu J, Xiao X, Chen Y, et al. ALKBH5/MAP3K8 axis regulates PD-L1+ macrophage infiltration and promotes hepatocellular carcinoma progression. Int J Biol Sci. 2022;18(13):5001–18.PubMedPubMedCentralCrossRef
69.
Sun Z, Su Z, Zhou Z, Wang S, Wang Z, Tong X, et al. RNA demethylase ALKBH5 inhibits TGF-β-induced EMT by regulating TGF-β/SMAD signaling in non-small cell lung cancer. Faseb j. 2022;36(5):e22283.PubMedCrossRef
70.
Tan B, Zhou K, Liu W, Prince E, Qing Y, Li Y, et al. RNA N(6) -methyladenosine reader YTHDC1 is essential for TGF-beta-mediated metastasis of triple negative breast cancer. Theranostics. 2022;12(13):5727–43.PubMedPubMedCentralCrossRef
71.
Hua W, Ten Dijke P, Kostidis S, Giera M, Hornsveld M. TGFβ-induced metabolic reprogramming during epithelial-to-mesenchymal transition in cancer. Cell Mol Life Sci. 2020;77(11):2103–23.PubMedCrossRef
72.
Liu Z, Zheng N, Li J, Li C, Zheng D, Jiang X, et al. N6-methyladenosine-modified circular RNA QSOX1 promotes colorectal cancer resistance to anti-CTLA-4 therapy through induction of intratumoral regulatory T cells. Drug Resist Updat. 2022;65:100886.PubMedCrossRef
73.
Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Cancer. 2011;11(2):85–95.PubMedCrossRef
74.
Bao Y, Zhai J, Chen H, Wong CC, Liang C, Ding Y, et al. Targeting m(6)A reader YTHDF1 augments antitumour immunity and boosts anti-PD-1 efficacy in colorectal cancer. Gut. 2023;72(8):1497–509.PubMedCrossRef
75.
Fiore PF, Di Matteo S, Tumino N, Mariotti FR, Pietra G, Ottonello S, et al. Interleukin-15 and cancer: some solved and many unsolved questions. J Immunother Cancer. 2020;8(2).
76.
Liu Y, Guo Q, Yang H, Zhang XW, Feng N, Wang JK, et al. Allosteric regulation of IGF2BP1 as a novel strategy for the activation of tumor immune microenvironment. ACS Cent Sci. 2022;8(8):1102–15.PubMedPubMedCentralCrossRef
77.
Bai X, Wong CC, Pan Y, Chen H, Liu W, Zhai J, et al. Loss of YTHDF1 in gastric tumors restores sensitivity to antitumor immunity by recruiting mature dendritic cells. J Immunother Cancer. 2022;10(2).
78.
Zhou B, Bie F, Zang R, Zhang M, Song P, Liu L, et al. RNA modification writer expression profiles predict clinical outcomes and guide neoadjuvant immunotherapy in non-small cell lung cancer. EBioMedicine. 2022;84:104268.PubMedPubMedCentralCrossRef
79.
Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018–28.PubMedCrossRef
80.
Pitt JM, Vétizou M, Daillère R, Roberti MP, Yamazaki T, Routy B, et al. Resistance mechanisms to immune-checkpoint blockade in cancer: tumor-intrinsic and -extrinsic factors. Immunity. 2016;44(6):1255–69.PubMedCrossRef
81.
82.
83.
Yankova E, Blackaby W, Albertella M, Rak J, De Braekeleer E, Tsagkogeorga G, et al. Small-molecule inhibition of METTL3 as a strategy against myeloid leukaemia. Nature. 2021;593(7860):597–601.PubMedPubMedCentralCrossRef
84.
Yu R, Wei Y, He C, Zhou P, Yang H, Deng C, et al. Integrative analyses of m6A regulators identify that METTL3 is associated with HPV status and immunosuppressive microenvironment in HPV-related cancers. Int J Biol Sci. 2022;18(9):3874–87.PubMedPubMedCentralCrossRef
85.
Su R, Dong L, Li Y, Gao M, Han L, Wunderlich M, et al. Targeting FTO suppresses cancer stem cell maintenance and immune evasion. Cancer Cell. 2020;38(1):79-96.e11.PubMedPubMedCentralCrossRef
86.
Liu Z, Zhong J, Zeng J, Duan X, Lu J, Sun X, et al. Characterization of the m6A-associated tumor immune microenvironment in prostate cancer to aid immunotherapy. Front Immunol. 2021;12:735170.PubMedPubMedCentralCrossRef
87.
Yang S, Wei J, Cui YH, Park G, Shah P, Deng Y, et al. m(6)A mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade. Nat Commun. 2019;10(1):2782.PubMedPubMedCentralCrossRef
88.
Chen B, Ye F, Yu L, Jia G, Huang X, Zhang X, et al. Development of cell-active N6-methyladenosine RNA demethylase FTO inhibitor. J Am Chem Soc. 2012;134(43):17963–71.PubMedCrossRef
89.
Huang Y, Yan J, Li Q, Li J, Gong S, Zhou H, et al. Meclofenamic acid selectively inhibits FTO demethylation of m6A over ALKBH5. Nucleic Acids Res. 2015;43(1):373–84.PubMedCrossRef
90.
Zheng G, Cox T, Tribbey L, Wang GZ, Iacoban P, Booher ME, et al. Synthesis of a FTO inhibitor with anticonvulsant activity. ACS Chem Neurosci. 2014;5(8):658–65.PubMedPubMedCentralCrossRef
91.
Wang T, Hong T, Huang Y, Su H, Wu F, Chen Y, et al. Fluorescein derivatives as bifunctional molecules for the simultaneous inhibiting and labeling of FTO protein. J Am Chem Soc. 2015;137(43):13736–9.PubMedCrossRef
92.
Su R, Dong L, Li C, Nachtergaele S, Wunderlich M, Qing Y, et al. R-2HG exhibits anti-tumor activity by targeting FTO/m(6)A/MYC/CEBPA signaling. Cell. 2018;172(1–2):90-105.e23.PubMedCrossRef
93.
Huang Y, Su R, Sheng Y, Dong L, Dong Z, Xu H, et al. Small-molecule targeting of oncogenic FTO demethylase in acute myeloid leukemia. Cancer Cell. 2019;35(4):677-91.e10.PubMedPubMedCentralCrossRef
94.
Xie G, Wu XN, Ling Y, Rui Y, Wu D, Zhou J, et al. A novel inhibitor of N (6)-methyladenosine demethylase FTO induces mRNA methylation and shows anti-cancer activities. Acta Pharm Sin B. 2022;12(2):853–66.PubMedCrossRef
95.
Chen J, Xu C, Yang K, Gao R, Cao Y, Liang L, et al. Inhibition of ALKBH5 attenuates I/R-induced renal injury in male mice by promoting Ccl28 m6A modification and increasing Treg recruitment. Nat Commun. 2023;14(1):1161.PubMedPubMedCentralCrossRef
96.
Fang Z, Mu B, Liu Y, Guo N, Xiong L, Guo Y, et al. Discovery of a potent, selective and cell active inhibitor of m(6)A demethylase ALKBH5. Eur J Med Chem. 2022;238:114446.PubMedCrossRef
97.
Wang YZ, Li HY, Zhang Y, Jiang RX, Xu J, Gu J, et al. Discovery of pyrazolo[1,5-a]pyrimidine derivative as a novel and selective ALKBH5 inhibitor for the treatment of AML. J Med Chem. 2023;66(23):15944–59.PubMedCrossRef
98.
Li N, Kang Y, Wang L, Huff S, Tang R, Hui H, et al. ALKBH5 regulates anti-PD-1 therapy response by modulating lactate and suppressive immune cell accumulation in tumor microenvironment. Proc Natl Acad Sci USA. 2020;117(33):20159–70.PubMedPubMedCentralCrossRef
99.
Ouyang Z, Gao Y, Yang R, Shen M, Shi X. Genetic engineering of dendritic cells using partially zwitterionic dendrimer-entrapped gold nanoparticles boosts efficient tumor immunotherapy. Biomacromol. 2022;23(3):1326–36.CrossRef
100.
Zhang X, Su T, Wu Y, Cai Y, Wang L, Liang C, et al. N6-methyladenosine reader YTHDF1 promotes stemness and therapeutic resistance in hepatocellular carcinoma by enhancing NOTCH1 expression. Cancer Res. 2024.
Metadaten
Titel
Role of m6A modifications in immune evasion and immunotherapy
verfasst von
Chunyu Wu
Lvyuan Li
Qiling Tang
Qianjin Liao
Pan Chen
Can Guo
Zhaoyang Zeng
Wei Xiong
Publikationsdatum
01.06.2024
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 6/2024
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-024-02402-9

Weitere Artikel der Ausgabe 6/2024

Medical Oncology 6/2024 Zur Ausgabe

Original Paper

CLIP170 inhibits the metastasis and EMT of papillary thyroid cancer through the TGF-β pathway

Original Paper

Combination of an aurora kinase inhibitor and the ABL tyrosine kinase inhibitor asciminib against ABL inhibitor-resistant CML cells

Letter to the Editor

The role of radiation therapy in locally advanced rectal cancer [In regard to primary surgery followed by selective chemoradiotherapy versus preoperative chemoradiotherapy followed by surgery for locally advanced rectal cancer: a randomized clinical trial]

Original Paper

Dermaseptin B2 bioactive gene’s potential for anticancer and anti-proliferative effect is linked to the regulation of the BAX/BBC3/AKT pathway

Original Article

Evaluation of the cytotoxic activities of the essential oil from Pistacia atlantica Desf. oleoresin on human gastric cancer cell lines

Original Paper

Rhein suppresses esophageal cancer development by regulating cell cycle through DNMT3B gene

Neu im Fachgebiet Onkologie

Bei seelischem Stress sind Checkpoint-Hemmer weniger wirksam

03.06.2024 NSCLC Nachrichten

Wie stark Menschen mit fortgeschrittenem NSCLC von einer Therapie mit Immun-Checkpoint-Hemmern profitieren, hängt offenbar auch davon ab, wie sehr die Diagnose ihre psychische Verfassung erschüttert

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

29.05.2024 Larynxkarzinom Nachrichten

Fast ein Viertel der Personen mit mäßig dysplastischen Stimmlippenläsionen entwickelt einen Kehlkopftumor. Solche Personen benötigen daher eine besonders enge ärztliche Überwachung.

15% bedauern gewählte Blasenkrebs-Therapie

29.05.2024 Urothelkarzinom Nachrichten

Ob Patienten und Patientinnen mit neu diagnostiziertem Blasenkrebs ein Jahr später Bedauern über die Therapieentscheidung empfinden, wird einer Studie aus England zufolge von der Radikalität und dem Erfolg des Eingriffs beeinflusst.

Erhöhtes Risiko fürs Herz unter Checkpointhemmer-Therapie

28.05.2024 Nebenwirkungen der Krebstherapie Nachrichten

Kardiotoxische Nebenwirkungen einer Therapie mit Immuncheckpointhemmern mögen selten sein – wenn sie aber auftreten, wird es für Patienten oft lebensgefährlich. Voruntersuchung und Monitoring sind daher obligat.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise