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image of Research Progress of M6A Methylation Modification in Immunotherapy of Colorectal Cancer

Abstract

Among the Poly(ADP-ribose) Polymerase (PARP) family in mammals, PARP1 is the first identified and well-studied member that plays a critical role in DNA damage repair and has been proven to be an effective target for cancer therapy. Here, we have reviewed not only the role of PARP1 in different DNA damage repair pathways, but also the working mechanisms of several PARP inhibitors (PARPi), inhibiting Poly-ADP-ribosylation (PARylation) processing and PAR chains production to trap PARP1 on impaired DNA and inducing Transcription-replication Conflicts (TRCs) by inhibiting the PARP1 activity. This review has systematically summarized the latest clinical application of six authorized PARPi, including olaparib, rucaparib, niraparib, talazoparib, fuzuloparib and pamiparib, in monotherapy and combination therapies with chemotherapy, radiotherapy, and immunotherapy, in different kinds of cancer. Furthermore, probable challenges in PARPi application and drug resistance mechanisms have also been discussed. Despite these challenges, further development of new PARP1 inhibitors appears promising as a valuable approach to cancer treatment.

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2025-03-06
2025-07-06
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References

  1. Biller L.H. Schrag D. Diagnosis and treatment of metastatic colorectal cancer. JAMA 2021 325 7 669 685 10.1001/jama.2021.0106 33591350
    [Google Scholar]
  2. Smyth E.C. Moehler M. Late-line treatment in metastatic gastric cancer: Today and tomorrow. Ther. Adv. Med. Oncol. 2019 11 1758835919867522 10.1177/1758835919867522 31489035
    [Google Scholar]
  3. Li B. Cui Y. Nambiar D.K. Sunwoo J.B. Li R. The immune subtypes and landscape of squamous cell carcinoma. Clin. Cancer Res. 2019 25 12 3528 3537 10.1158/1078‑0432.CCR‑18‑4085 30833271
    [Google Scholar]
  4. Topalian S.L. Drake C.G. Pardoll D.M. Immune checkpoint blockade: A common denominator approach to cancer therapy. Cancer Cell 2015 27 4 450 461 10.1016/j.ccell.2015.03.001 25858804
    [Google Scholar]
  5. Zhao B.S. Roundtree I.A. He C. Post-transcriptional gene regulation by mRNA modifications. Nat. Rev. Mol. Cell Biol. 2017 18 1 31 42 10.1038/nrm.2016.132 27808276
    [Google Scholar]
  6. Zhao Y. Peng H. The role of N6-Methyladenosine (m6A) methylation modifications in hematological malignancies. Cancers 2022 14 2 332 10.3390/cancers14020332 35053496
    [Google Scholar]
  7. Umuhire Juru A. Hargrove A.E. Frameworks for targeting RNA with small molecules. J. Biol. Chem. 2021 296 100191 10.1074/jbc.REV120.015203 33334887
    [Google Scholar]
  8. Khan R.I.N. Malla W.A. m6A modification of RNA and its role in cancer, with a special focus on lung cancer. Genomics 2021 113 4 2860 2869 10.1016/j.ygeno.2021.06.013 34118382
    [Google Scholar]
  9. Li X.C. Jin F. Wang B.Y. Yin X.J. Hong W. Tian F.J. The m6A demethylase ALKBH5 controls trophoblast invasion at the maternal-fetal interface by regulating the stability of CYR61 mRNA. Theranostics 2019 9 13 3853 3865 10.7150/thno.31868 31281518
    [Google Scholar]
  10. Chen Z. Wu L. Zhou J. Lin X. Peng Y. Ge L. Chiang C.M. Huang H. Wang H. He W. N6 -methyladenosine-induced ERRγ triggers chemoresistance of cancer cells through upregulation of ABCB1 and metabolic reprogramming. Theranostics 2020 10 8 3382 3396 10.7150/thno.40144 32206097
    [Google Scholar]
  11. Chen X.Y. Zhang J. Zhu J.S. The role of m6A RNA methylation in human cancer. Mol. Cancer 2019 18 1 103 10.1186/s12943‑019‑1033‑z 31142332
    [Google Scholar]
  12. Shulman Z. Stern-Ginossar N. The RNA modification N6-methyladenosine as a novel regulator of the immune system. Nat. Immunol. 2020 21 5 501 512 10.1038/s41590‑020‑0650‑4 32284591
    [Google Scholar]
  13. Zhao Q. Zhao Y. Hu W. Zhang Y. Wu X. Lu J. Li M. Li W. Wu W. Wang J. Du F. Ji H. Yang X. Xu Z. Wan L. Wen Q. Li X. Cho C.H. Zou C. Shen J. Xiao Z. m 6 A RNA modification modulates PI3K/Akt/mTOR signal pathway in gastrointestinal cancer. Theranostics 2020 10 21 9528 9543 10.7150/thno.42971 32863943
    [Google Scholar]
  14. Wang Y. Wang Y. Luo W. Song X. Huang L. Xiao J. Jin F. Ren Z. Wang Y. Roles of long non-coding RNAs and emerging RNA-binding proteins in innate antiviral responses. Theranostics 2020 10 20 9407 9424 10.7150/thno.48520 32802200
    [Google Scholar]
  15. Li Y. Xiao J. Bai J. Tian Y. Qu Y. Chen X. Wang Q. Li X. Zhang Y. Xu J. Molecular characterization and clinical relevance of m6A regulators across 33 cancer types. Mol. Cancer 2019 18 1 137 10.1186/s12943‑019‑1066‑3 31521193
    [Google Scholar]
  16. Meyer K.D. Jaffrey S.R. Rethinking m 6 A readers, writers, and erasers. Annu. Rev. Cell Dev. Biol. 2017 33 1 319 342 10.1146/annurev‑cellbio‑100616‑060758 28759256
    [Google Scholar]
  17. Liang Z. Kidwell R.L. Deng H. Xie Q. Epigenetic N6-methyladenosine modification of RNA and DNA regulates cancer. Cancer Biol. Med. 2020 17 1 9 19 10.20892/j.issn.2095‑3941.2019.0347 32296573
    [Google Scholar]
  18. Zhu T. Roundtree I.A. Wang P. Wang X. Wang L. Sun C. Tian Y. Li J. He C. Xu Y. Crystal structure of the YTH domain of YTHDF2 reveals mechanism for recognition of N6-methyladenosine. Cell Res. 2014 24 12 1493 1496 10.1038/cr.2014.152 25412661
    [Google Scholar]
  19. Huang H. Weng H. Sun W. Qin X. Shi H. Wu H. Zhao B.S. Mesquita A. Liu C. Yuan C.L. Hu Y.C. Hüttelmaier S. Skibbe J.R. Su R. Deng X. Dong L. Sun M. Li C. Nachtergaele S. Wang Y. Hu C. Ferchen K. Greis K.D. Jiang X. Wei M. Qu L. Guan J.L. He C. Yang J. Chen J. Recognition of RNA N6-methyladenosine by IGF2BP proteins enhances mRNA stability and translation. Nat. Cell Biol. 2018 20 3 285 295 10.1038/s41556‑018‑0045‑z 29476152
    [Google Scholar]
  20. Alarcón C.R. Lee H. Goodarzi H. Halberg N. Tavazoie S.F. N6-methyladenosine marks primary microRNAs for processing. Nature 2015 519 7544 482 485 10.1038/nature14281 25799998
    [Google Scholar]
  21. Wang X. Zhao B.S. Roundtree I.A. Lu Z. Han D. Ma H. Weng X. Chen K. Shi H. He C. N6-methyladenosine modulates messenger RNA translation efficiency. Cell 2015 161 6 1388 1399 10.1016/j.cell.2015.05.014 26046440
    [Google Scholar]
  22. Du H. Zhao Y. He J. Zhang Y. Xi H. Liu M. Ma J. Wu L. YTHDF2 destabilizes m6A-containing RNA through direct recruitment of the CCR4–NOT deadenylase complex. Nat. Commun. 2016 7 1 12626 10.1038/ncomms12626 27558897
    [Google Scholar]
  23. Mahajan U.M. Langhoff E. Goni E. Costello E. Greenhalf W. Halloran C. Ormanns S. Kruger S. Boeck S. Ribback S. Beyer G. Dombroswki F. Weiss F.U. Neoptolemos J.P. Werner J. D’Haese J.G. Bazhin A. Peterhansl J. Pichlmeier S. Büchler M.W. Kleeff J. Ganeh P. Sendler M. Palmer D.H. Kohlmann T. Rad R. Regel I. Lerch M.M. Mayerle J. Immune cell and stromal signature associated with progression-free survival of patients with resected pancreatic ductal adenocarcinoma. Gastroenterology 2018 155 5 1625 1639.e2 10.1053/j.gastro.2018.08.009 30092175
    [Google Scholar]
  24. Fridman W.H. Zitvogel L. Sautès-Fridman C. Kroemer G. The immune contexture in cancer prognosis and treatment. Nat. Rev. Clin. Oncol. 2017 14 12 717 734 10.1038/nrclinonc.2017.101 28741618
    [Google Scholar]
  25. Turley S.J. Cremasco V. Astarita J.L. Immunological hallmarks of stromal cells in the tumour microenvironment. Nat. Rev. Immunol. 2015 15 11 669 682 10.1038/nri3902 26471778
    [Google Scholar]
  26. Sun Q. Zhang B. Hu Q. Qin Y. Xu W. Liu W. Yu X. Xu J. The impact of cancer-associated fibroblasts on major hallmarks of pancreatic cancer. Theranostics 2018 8 18 5072 5087 10.7150/thno.26546 30429887
    [Google Scholar]
  27. Pagès F. Mlecnik B. Marliot F. Bindea G. Ou F.S. Bifulco C. Lugli A. Zlobec I. Rau T.T. Berger M.D. Nagtegaal I.D. Vink-Börger E. Hartmann A. Geppert C. Kolwelter J. Merkel S. Grützmann R. Van den Eynde M. Jouret-Mourin A. Kartheuser A. Léonard D. Remue C. Wang J.Y. Bavi P. Roehrl M.H.A. Ohashi P.S. Nguyen L.T. Han S. MacGregor H.L. Hafezi-Bakhtiari S. Wouters B.G. Masucci G.V. Andersson E.K. Zavadova E. Vocka M. Spacek J. Petruzelka L. Konopasek B. Dundr P. Skalova H. Nemejcova K. Botti G. Tatangelo F. Delrio P. Ciliberto G. Maio M. Laghi L. Grizzi F. Fredriksen T. Buttard B. Angelova M. Vasaturo A. Maby P. Church S.E. Angell H.K. Lafontaine L. Bruni D. El Sissy C. Haicheur N. Kirilovsky A. Berger A. Lagorce C. Meyers J.P. Paustian C. Feng Z. Ballesteros-Merino C. Dijkstra J. van de Water C. van Lent-van Vliet S. Knijn N. Mușină A.M. Scripcariu D.V. Popivanova B. Xu M. Fujita T. Hazama S. Suzuki N. Nagano H. Okuno K. Torigoe T. Sato N. Furuhata T. Takemasa I. Itoh K. Patel P.S. Vora H.H. Shah B. Patel J.B. Rajvik K.N. Pandya S.J. Shukla S.N. Wang Y. Zhang G. Kawakami Y. Marincola F.M. Ascierto P.A. Sargent D.J. Fox B.A. Galon J. International validation of the consensus immunoscore for the classification of colon cancer: A prognostic and accuracy study. Lancet 2018 391 10135 2128 2139 10.1016/S0140‑6736(18)30789‑X 29754777
    [Google Scholar]
  28. Le D.T. Durham J.N. Smith K.N. Wang H. Bartlett B.R. Aulakh L.K. Lu S. Kemberling H. Wilt C. Luber B.S. Wong F. Azad N.S. Rucki A.A. Laheru D. Donehower R. Zaheer A. Fisher G.A. Crocenzi T.S. Lee J.J. Greten T.F. Duffy A.G. Ciombor K.K. Eyring A.D. Lam B.H. Joe A. Kang S.P. Holdhoff M. Danilova L. Cope L. Meyer C. Zhou S. Goldberg R.M. Armstrong D.K. Bever K.M. Fader A.N. Taube J. Housseau F. Spetzler D. Xiao N. Pardoll D.M. Papadopoulos N. Kinzler K.W. Eshleman J.R. Vogelstein B. Anders R.A. Diaz L.A. Jr Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 2017 357 6349 409 413 10.1126/science.aan6733 28596308
    [Google Scholar]
  29. Xiao Y. Freeman G.J. The microsatellite instable subset of colorectal cancer is a particularly good candidate for checkpoint blockade immunotherapy. Cancer Discov. 2015 5 1 16 18 10.1158/2159‑8290.CD‑14‑1397 25583798
    [Google Scholar]
  30. Galon J. Bruni D. Approaches to treat immune hot, altered and cold tumours with combination immunotherapies. Nat. Rev. Drug Discov. 2019 18 3 197 218 10.1038/s41573‑018‑0007‑y 30610226
    [Google Scholar]
  31. Binnewies M. Roberts E.W. Kersten K. Chan V. Fearon D.F. Merad M. Coussens L.M. Gabrilovich D.I. Ostrand-Rosenberg S. Hedrick C.C. Vonderheide R.H. Pittet M.J. Jain R.K. Zou W. Howcroft T.K. Woodhouse E.C. Weinberg R.A. Krummel M.F. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat. Med. 2018 24 5 541 550 10.1038/s41591‑018‑0014‑x 29686425
    [Google Scholar]
  32. Li X. Wen D. Li X. Yao C. Chong W. Chen H. Identification of an immune signature predicting prognosis risk and lymphocyte infiltration in colon cancer. Front. Immunol. 2020 11 1678 10.3389/fimmu.2020.01678 33013820
    [Google Scholar]
  33. Camus M. Tosolini M. Mlecnik B. Pagès F. Kirilovsky A. Berger A. Costes A. Bindea G. Charoentong P. Bruneval P. Trajanoski Z. Fridman W.H. Galon J. Coordination of intratumoral immune reaction and human colorectal cancer recurrence. Cancer Res. 2009 69 6 2685 2693 10.1158/0008‑5472.CAN‑08‑2654 19258510
    [Google Scholar]
  34. Hegde P.S. Karanikas V. Evers S. The where, the when, and the how of immune monitoring for cancer immunotherapies in the era of checkpoint inhibition. Clin. Cancer Res. 2016 22 8 1865 1874 10.1158/1078‑0432.CCR‑15‑1507 27084740
    [Google Scholar]
  35. Chen D.S. Mellman I. nlms of cancer immunity and the cancer–immune set point. Nature 2017 541 7637 321 330 10.1038/nature21349 28102259
    [Google Scholar]
  36. Mlecnik B. Tosolini M. Kirilovsky A. Berger A. Bindea G. Meatchi T. Bruneval P. Trajanoski Z. Fridman W.H. Pagès F. Galon J. Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J. Clin. Oncol. 2011 29 6 610 618 10.1200/JCO.2010.30.5425 21245428
    [Google Scholar]
  37. Mariathasan S. Turley S.J. Nickles D. Castiglioni A. Yuen K. Wang Y. Kadel E.E. III Koeppen H. Astarita J.L. Cubas R. Jhunjhunwala S. Banchereau R. Yang Y. Guan Y. Chalouni C. Ziai J. Şenbabaoğlu Y. Santoro S. Sheinson D. Hung J. Giltnane J.M. Pierce A.A. Mesh K. Lianoglou S. Riegler J. Carano R.A.D. Eriksson P. Höglund M. Somarriba L. Halligan D.L. van der Heijden M.S. Loriot Y. Rosenberg J.E. Fong L. Mellman I. Chen D.S. Green M. Derleth C. Fine G.D. Hegde P.S. Bourgon R. Powles T. TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature 2018 554 7693 544 548 10.1038/nature25501 29443960
    [Google Scholar]
  38. Han D. Liu J. Chen C. Dong L. Liu Y. Chang R. Huang X. Liu Y. Wang J. Dougherty U. Bissonnette M.B. Shen B. Weichselbaum R.R. Xu M.M. He C. Anti-tumour immunity controlled through mRNA m6A methylation and YTHDF1 in dendritic cells. Nature 2019 566 7743 270 274 10.1038/s41586‑019‑0916‑x 30728504
    [Google Scholar]
  39. Yang S. Wei J. Cui Y.H. Park G. Shah P. Deng Y. Aplin A.E. Lu Z. Hwang S. He C. He Y.Y. m6A mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade. Nat. Commun. 2019 10 1 2782 10.1038/s41467‑019‑10669‑0 31239444
    [Google Scholar]
  40. Wang H. Hu X. Huang M. Liu J. Gu Y. Ma L. Zhou Q. Cao X. Mettl3-mediated mRNA m6A methylation promotes dendritic cell activation. Nat. Commun. 2019 10 1 1898 10.1038/s41467‑019‑09903‑6 31015515
    [Google Scholar]
  41. Lewinska A. Adamczyk-Grochala J. Deregowska A. Wnuk M. Sulforaphane-induced cell cycle arrest and senescence are accompanied by dna hypomethylation and changes in microRNA profile in breast cancer cells. Theranostics 2017 7 14 3461 3477 10.7150/thno.20657 28912888
    [Google Scholar]
  42. Chen Y.T. Shen J.Y. Chen D.P. Wu C.F. Guo R. Zhang P.P. Lv J.W. Li W.F. Wang Z.X. Chen Y.P. Identification of cross-talk between m6A and 5mC regulators associated with onco-immunogenic features and prognosis across 33 cancer types. J. Hematol. Oncol. 2020 13 1 22 10.1186/s13045‑020‑00854‑w 32188475
    [Google Scholar]
  43. Finotello F. Trajanoski Z. Quantifying tumor-infiltrating immune cells from transcriptomics data. Cancer Immunol. Immunother. 2018 67 7 1031 1040 10.1007/s00262‑018‑2150‑z 29541787
    [Google Scholar]
  44. Gu Y. Wu X. Zhang J. Fang Y. Pan Y. Shu Y. Ma P. The evolving landscape of N6-methyladenosine modification in the tumor microenvironment. Mol. Ther. 2021 29 5 1703 1715 10.1016/j.ymthe.2021.04.009 33839323
    [Google Scholar]
  45. Wang X. Feng J. Xue Y. Guan Z. Zhang D. Liu Z. Gong Z. Wang Q. Huang J. Tang C. Zou T. Yin P. Correction: Corrigendum: Structural basis of N6-adenosine methylation by the METTL3–METTL14 complex. Nature 2017 542 7640 260 10.1038/nature21073 28099411
    [Google Scholar]
  46. Aas P.A. Otterlei M. Falnes P.Ø. Vågbø C.B. Skorpen F. Akbari M. Sundheim O. Bjørås M. Slupphaug G. Seeberg E. Krokan H.E. Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA. Nature 2003 421 6925 859 863 10.1038/nature01363 12594517
    [Google Scholar]
  47. Wang T. Kong S. Tao M. Ju S. The potential role of RNA N6-methyladenosine in cancer progression. Mol. Cancer 2020 19 1 88 10.1186/s12943‑020‑01204‑7 32398132
    [Google Scholar]
  48. Jian D. Wang Y. Jian L. Tang H. Rao L. Chen K. Jia Z. Zhang W. Liu Y. Chen X. Shen X. Gao C. Wang S. Li M. METTL14 aggravates endothelial inflammation and atherosclerosis by increasing FOXO1 N6-methyladeosine modifications. Theranostics 2020 10 20 8939 8956 10.7150/thno.45178 32802173
    [Google Scholar]
  49. Topalian S.L. Taube J.M. Anders R.A. Pardoll D.M. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat. Rev. Cancer 2016 16 5 275 287 10.1038/nrc.2016.36 27079802
    [Google Scholar]
  50. Zeng D. Ye Z. Wu J. Zhou R. Fan X. Wang G. Huang Y. Wu J. Sun H. Wang M. Bin J. Liao Y. Li N. Shi M. Liao W. Macrophage correlates with immunophenotype and predicts anti-PD-L1 response of urothelial cancer. Theranostics 2020 10 15 7002 7014 10.7150/thno.46176 32550918
    [Google Scholar]
  51. Tauriello D.V.F. Palomo-Ponce S. Stork D. Berenguer-Llergo A. Badia-Ramentol J. Iglesias M. Sevillano M. Ibiza S. Cañellas A. Hernando-Momblona X. Byrom D. Matarin J.A. Calon A. Rivas E.I. Nebreda A.R. Riera A. Attolini C.S.O. Batlle E. TGFβ drives immune evasion in genetically reconstituted colon cancer metastasis. Nature 2018 554 7693 538 543 10.1038/nature25492 29443964
    [Google Scholar]
  52. Panagi M. Voutouri C. Mpekris F. Papageorgis P. Martin M.R. Martin J.D. Demetriou P. Pierides C. Polydorou C. Stylianou A. Louca M. Koumas L. Costeas P. Kataoka K. Cabral H. Stylianopoulos T. TGF-β inhibition combined with cytotoxic nanomedicine normalizes triple negative breast cancer microenvironment towards anti-tumor immunity. Theranostics 2020 10 4 1910 1922 10.7150/thno.36936 32042344
    [Google Scholar]
  53. Chong W. Shang L. Liu J. Fang Z. Du F. Wu H. Liu Y. Wang Z. Chen Y. Jia S. Chen L. Li L. Chen H. m 6 A regulator-based methylation modification patterns characterized by distinct tumor microenvironment immune profiles in colon cancer. Theranostics 2021 11 5 2201 2217 10.7150/thno.52717 33500720
    [Google Scholar]
  54. Takaba H. Takayanagi H. The mechanisms of T cell selection in the thymus. Trends Immunol. 2017 38 11 805 816 10.1016/j.it.2017.07.010 28830733
    [Google Scholar]
  55. Li H.B. Tong J. Zhu S. Batista P.J. Duffy E.E. Zhao J. Bailis W. Cao G. Kroehling L. Chen Y. Wang G. Broughton J.P. Chen Y.G. Kluger Y. Simon M.D. Chang H.Y. Yin Z. Flavell R.A. m6A mRNA methylation controls T cell homeostasis by targeting the IL-7/STAT5/SOCS pathways. Nature 2017 548 7667 338 342 10.1038/nature23450 28792938
    [Google Scholar]
  56. Crotty S. T follicular helper cell biology: A decade of discovery and diseases. Immunity 2019 50 5 1132 1148 10.1016/j.immuni.2019.04.011 31117010
    [Google Scholar]
  57. Yao Y. Yang Y. Guo W. Xu L. You M. Zhang Y.C. Sun Z. Cui X. Yu G. Qi Z. Liu J. Wang F. Liu J. Zhao T. Ye L. Yang Y.G. Yu S. METTL3-dependent m6A modification programs T follicular helper cell differentiation. Nat. Commun. 2021 12 1 1333 10.1038/s41467‑021‑21594‑6 33637761
    [Google Scholar]
  58. Tong J. Cao G. Zhang T. Sefik E. Amezcua Vesely M.C. Broughton J.P. Zhu S. Li H. Li B. Chen L. Chang H.Y. Su B. Flavell R.A. Li H.B. m6A mRNA methylation sustains Treg suppressive functions. Cell Res. 2018 28 2 253 256 10.1038/cr.2018.7 29303144
    [Google Scholar]
  59. Liu Z. Wang T. She Y. Wu K. Gu S. Li L. Dong C. Chen C. Zhou Y. N6-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 10.1186/s12943‑021‑01398‑4 34416901
    [Google Scholar]
  60. Dong L. Chen C. Zhang Y. Guo P. Wang Z. Li J. Liu Y. Liu J. Chang R. Li Y. Liang G. Lai W. Sun M. Dougherty U. Bissonnette M.B. Wang H. Shen L. Xu M.M. Han D. The loss of RNA N6-adenosine methyltransferase Mettl14 in tumor-associated macrophages promotes CD8+ T cell dysfunction and tumor growth. Cancer Cell 2021 39 7 945 957.e10 10.1016/j.ccell.2021.04.016 34019807
    [Google Scholar]
  61. Lu T.X. Zheng Z. Zhang L. Sun H.L. Bissonnette M. Huang H. He C. A New model of spontaneous colitis in mice induced by deletion of an RNA m6A methyltransferase component METTL14 in T cells. Cell. Mol. Gastroenterol. Hepatol. 2020 10 4 747 761 10.1016/j.jcmgh.2020.07.001 32634481
    [Google Scholar]
  62. Zhou J. Zhang X. Hu J. Qu R. Yu Z. Xu H. Chen H. Yan L. Ding C. Zou Q. Ye Y. Wang Z. Flavell R.A. Li H.B. m 6 A demethylase ALKBH5 controls CD4 + T cell pathogenicity and promotes autoimmunity. Sci. Adv. 2021 7 25 eabg0470 10.1126/sciadv.abg0470 34134995
    [Google Scholar]
  63. Ding C. Xu H. Yu Z. Roulis M. Qu R. Zhou J. Oh J. Crawford J. Gao Y. Jackson R. Sefik E. Li S. Wei Z. Skadow M. Yin Z. Ouyang X. Wang L. Zou Q. Su B. Hu W. Flavell R.A. Li H.B. RNA m 6 A demethylase ALKBH5 regulates the development of γδ T cells. Proc. Natl. Acad. Sci. USA 2022 119 33 e2203318119 10.1073/pnas.2203318119 35939687
    [Google Scholar]
  64. Huang H. Zhang G. Ruan G.X. Li Y. Chen W. Zou J. Zhang R. Wang J. Ji S.J. Xu S. Ou X. Mettl14-mediated m6A modification is essential for germinal center B cell response. J. Immunol. 2022 208 8 1924 1936 10.4049/jimmunol.2101071 35365563
    [Google Scholar]
  65. Zheng Z. Zhang L. Cui X.L. Yu X. Hsu P.J. Lyu R. Tan H. Mandal M. Zhang M. Sun H.L. Sanchez Castillo A. Peng J. Clark M.R. He C. Huang H. Control of early B cell development by the RNA N6-Methyladenosine methylation. Cell Rep. 2020 31 13 107819 10.1016/j.celrep.2020.107819 32610122
    [Google Scholar]
  66. Kang X. Chen S. Pan L. Liang X. Lu D. Chen H. Li Y. Liu C. Ge M. Zhang Q. Liu Q. Xu Y. Deletion of Mettl3 at the Pro-B stage marginally affects B Cell development and profibrogenic activity of B cells in liver fibrosis. J. Immunol. Res. 2022 2022 1 17 10.1155/2022/8118577 35747688
    [Google Scholar]
  67. Noy R. Pollard J.W. Tumor-associated macrophages: From mechanisms to therapy. Immunity 2014 41 1 49 61 10.1016/j.immuni.2014.06.010 25035953
    [Google Scholar]
  68. Tong J. Wang X. Liu Y. Ren X. Wang A. Chen Z. Yao J. Mao K. Liu T. Meng F.L. Pan W. Zou Q. Liu J. Zhou Y. Xia Q. Flavell R.A. Zhu S. Li H.B. Pooled CRISPR screening identifies m 6 A as a positive regulator of macrophage activation. Sci. Adv. 2021 7 18 eabd4742 10.1126/sciadv.abd4742 33910903
    [Google Scholar]
  69. Wang X. Ji Y. Feng P. Liu R. Li G. Zheng J. Xue Y. Wei Y. Ji C. Chen D. Li J. The m6A reader IGF2BP2 regulates macrophage phenotypic activation and inflammatory diseases by stabilizing TSC1 and PPAR γ. Adv. Sci. (Weinh.) 2021 8 13 2100209 10.1002/advs.202100209 34258163
    [Google Scholar]
  70. Guo M. Yan R. Ji Q. Yao H. Sun M. Duan L. Xue Z. Jia Y. IFN regulatory factor-1 induced macrophage pyroptosis by modulating m6A modification of circ_0029589 in patients with acute coronary syndrome. Int. Immunopharmacol. 2020 86 106800 10.1016/j.intimp.2020.106800 32674051
    [Google Scholar]
  71. Sun Z. Chen W. Wang Z. Wang S. Zan J. Zheng L. Zhao W. Matr3 reshapes m6A modification complex to alleviate macrophage inflammation during atherosclerosis. Clin. Immunol. 2022 245 109176 10.1016/j.clim.2022.109176 36368640
    [Google Scholar]
  72. Zhou K. Cheng T. Zhan J. Peng X. Zhang Y. Wen J. Chen X. Ying M. Targeting tumor associated macrophages in the tumor microenvironment (Review). Oncol. Lett. 2020 20 5 1 10.3892/ol.2020.12097 32968456
    [Google Scholar]
  73. Liu Y. Liu Z. Tang H. Shen Y. Gong Z. Xie N. Zhang X. Wang W. Kong W. Zhou Y. Fu Y. The N6 -methyladenosine (m 6 A)-forming enzyme METTL3 facilitates M1 macrophage polarization through the methylation of STAT1 mRNA. Am. J. Physiol. Cell Physiol. 2019 317 4 C762 C775 10.1152/ajpcell.00212.2019 31365297
    [Google Scholar]
  74. Yin H. Zhang X. Yang P. Zhang X. Peng Y. Li D. Yu Y. Wu Y. Wang Y. Zhang J. Ding X. Wang X. Yang A. Zhang R. RNA m6A methylation orchestrates cancer growth and metastasis via macrophage reprogramming. Nat. Commun. 2021 12 1 1394 10.1038/s41467‑021‑21514‑8 33654093
    [Google Scholar]
  75. Shi B. Liu W.W. Yang K. Jiang G.M. Wang H. The role, mechanism, and application of RNA methyltransferase METTL14 in gastrointestinal cancer. Mol. Cancer 2022 21 1 163 10.1186/s12943‑022‑01634‑5 35974338
    [Google Scholar]
  76. Liu Y. Shi M. He X. Cao Y. Liu P. Li F. Zou S. Wen C. Zhan Q. Xu Z. Wang J. Sun B. Shen B. 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 10.1186/s13045‑022‑01272‑w 35526050
    [Google Scholar]
  77. Morvan M.G. Lanier L.L. NK cells and cancer: You can teach innate cells new tricks. Nat. Rev. Cancer 2016 16 1 7 19 10.1038/nrc.2015.5 26694935
    [Google Scholar]
  78. Spits H. Bernink J.H. Lanier L. NK cells and type 1 innate lymphoid cells: Partners in host defense. Nat. Immunol. 2016 17 7 758 764 10.1038/ni.3482 27328005
    [Google Scholar]
  79. Ma S. Yan J. Barr T. Zhang J. Chen Z. Wang L.S. Sun J.C. Chen J. Caligiuri M.A. Yu J. The RNA m6A reader YTHDF2 controls NK cell antitumor and antiviral immunity. J. Exp. Med. 2021 218 8 e20210279 10.1084/jem.20210279 34160549
    [Google Scholar]
  80. Song H. Song J. Cheng M. Zheng M. Wang T. Tian S. Flavell R.A. Zhu S. Li H.B. Ding C. Wei H. Sun R. Peng H. Tian Z. METTL3-mediated m6A RNA methylation promotes the anti-tumour immunity of natural killer cells. Nat. Commun. 2021 12 1 5522 10.1038/s41467‑021‑25803‑0 34535671
    [Google Scholar]
  81. Steinman R.M. Banchereau J. Taking dendritic cells into medicine. Nature 2007 449 7161 419 426 10.1038/nature06175 17898760
    [Google Scholar]
  82. Wu H. Xu Z. Wang Z. Ren Z. Li L. Ruan Y. Dendritic cells with METTL3 gene knockdown exhibit immature properties and prolong allograft survival. Genes Immun. 2020 21 3 193 202 10.1038/s41435‑020‑0099‑3 32457372
    [Google Scholar]
  83. Cheng Y. Zhang T. Xu Q. Therapeutic advances in non-small cell lung cancer: Focus on clinical development of targeted therapy and immunotherapy. J. Med. Comm 2020 2 4 692
    [Google Scholar]
  84. Gou Q. Dong C. Xu H. Khan B. Jin J. Liu Q. Shi J. Hou Y. PD-L1 degradation pathway and immunotherapy for cancer. Cell Death Dis. 2020 11 11 955 10.1038/s41419‑020‑03140‑2 33159034
    [Google Scholar]
  85. Wang L. Hui H. Agrawal K. Kang Y. Li N. Tang R. Yuan J. Rana T.M. m 6 A RNA methyltransferases METTL3/14 regulate immune responses to anti‐PD‐1 therapy. EMBO J. 2020 39 20 e104514 10.15252/embj.2020104514 32964498
    [Google Scholar]
  86. Tong H. Wei H. Smith A.O. Huang J. The role of m6A epigenetic modification in the treatment of colorectal cancer immune checkpoint inhibitors. Front. Immunol. 2022 12 802049 10.3389/fimmu.2021.802049 35069586
    [Google Scholar]
  87. Zhang M. Song J. Yuan W. Zhang W. Sun Z. Roles of RNA methylation on tumor immunity and clinical implications. Front. Immunol. 2021 12 641507 10.3389/fimmu.2021.641507 33777035
    [Google Scholar]
  88. Lichtenstern C.R. Ngu R.K. Shalapour S. Karin M. Immunotherapy, inflammation and colorectal cancer. Cells 2020 9 3 618 10.3390/cells9030618 32143413
    [Google Scholar]
  89. Jiang Z. Zhang Y. Chen K. Yang X. Liu J. Integrated analysis of the immune infiltrates and PD-L1 expression of N6-methyladenosine-related long non-coding RNAs in colorectal cancer. Int. J. Gen. Med. 2021 14 5017 5028 10.2147/IJGM.S327765 34511985
    [Google Scholar]
  90. Cai C. Long J. Huang Q. Han Y. Peng Y. Guo C. Liu S. Chen Y. Shen E. Long K. Wang X. Yu J. Shen H. Zeng S. M6A “Writer” gene METTL14: A favorable prognostic biomarker and correlated with immune infiltrates in rectal cancer. Front. Oncol. 2021 11 615296 10.3389/fonc.2021.615296 34221955
    [Google Scholar]
  91. Zhou Y. Zhou H. Shi J. Guan A. Zhu Y. Hou Z. Li R. Decreased m6A modification of CD34/CD276(B7-H3) leads to immune escape in colon cancer. Front. Cell Dev. Biol. 2021 9 715674 10.3389/fcell.2021.715674 34307389
    [Google Scholar]
  92. Zhao C. Liu Y. Ju S. Wang X. Pan-cancer analysis of the N6-Methyladenosine eraser FTO as a potential prognostic and immunological biomarker. Int. J. Gen. Med. 2021 14 7411 7422 10.2147/IJGM.S331752 34744452
    [Google Scholar]
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  • Article Type:
    Review Article
Keywords: m6A ; Methylation ; Colorectal cancer ; Tumor immunotherapy
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