Epigenetic Mechanisms Driving Tumor Supportive Microenvironment Differentiation and Function: A Role in Cancer Therapy?

References

• Slack JMW . Conrad Hal Waddington: the last Renaissance biologist?Nat. Rev. Genet.3, 889–895 (2002) Nature Publishing Group.
   PubMed Web of Science ®Google Scholar
• Goldberg AD , AllisCD , BernsteinE. Epigenetics: a landscape takes shape. Cell128(4), 635–638 (2007).
   PubMed Web of Science ®Google Scholar
• Allis CD , JenuweinT. The molecular hallmarks of epigenetic control. Nat. Rev. Genet.17(8), 487–500 (2016).
   PubMed Web of Science ®Google Scholar
• Dzobo K . Epigenomics-guided drug development: recent advances in solving the cancer treatment “jigsaw puzzle”. OMICS23(2), 70–85 (2019).
   PubMed Web of Science ®Google Scholar
• Esteller M . Epigenetic drugs: more than meets the eye. Epigenetics12(5), 307–307 (2017).
   PubMed Web of Science ®Google Scholar
• Schübeler D . Function and information content of DNA methylation. Nature517(7534), 321–326 (2015).
   PubMed Web of Science ®Google Scholar
• Zhou VW , GorenA , BernsteinBE. Charting histone modifications and the functional organization of mammalian genomes. Nat. Rev. Genet.12(1), 7–18 (2011).
   PubMed Web of Science ®Google Scholar
• Kouzarides T . Chromatin modifications and their function. Cell128(4), 693–705 (2007).
   PubMed Web of Science ®Google Scholar
• Michalak EM , BurrML , BannisterAJ , DawsonMA. The roles of DNA, RNA and histone methylation in ageing and cancer. Nat. Rev. Mol. Cell Biol.150(6), 12–17 (2019).
   Google Scholar
• Ambros V . The functions of animal microRNAs. Nature431(7006), 350–355 (2004).
   PubMed Web of Science ®Google Scholar
• Fernandes JCR , AcuñaSM , AokiJI , Floeter-WinterLM , MuxelSM. Long non-coding RNAs in the regulation of gene expression: physiology and disease. Noncoding RNA5(1), 17 (2019).
   PubMed Web of Science ®Google Scholar
• Sun Y-C , WangY-Y , GeW , ChengS-F , DycePW , ShenW. Epigenetic regulation during the differentiation of stem cells to germ cells. Oncotarget8(34), 57836–57844 (2017).
   PubMedGoogle Scholar
• V Subramaniam A , YehyaAHS , ChengWK , WangX , OonCE. Epigenetics: the master control of endothelial cell fate in cancer. Life Sci.232, 116652 (2019).
   PubMed Web of Science ®Google Scholar
• Jambhekar A , DhallA , ShiY. Roles and regulation of histone methylation in animal development. Nat. Rev. Mol. Cell Biol.403, 1–17 (2019).
   Google Scholar
• Du H , CheG. Genetic alterations and epigenetic alterations of cancer-associated fibroblasts. Oncol. Lett.13(1), 3–12 (2017).
   PubMed Web of Science ®Google Scholar
• Liu M , ZhouJ , ChenZ , ChengAS-L. Understanding the epigenetic regulation of tumours and their microenvironments: opportunities and problems for epigenetic therapy. J. Pathol.241(1), 10–24 (2017).
   PubMed Web of Science ®Google Scholar
• Marks DL , OlsonRL , Fernandez-ZapicoME. Epigenetic control of the tumor microenvironment. 8(12), 1671–1687 (2016).
   Google Scholar
• Pidsley R , LawrenceMG , ZotenkoEet al. Enduring epigenetic landmarks define the cancer microenvironment. Genome Res.28(5), 625–638 (2018).
   PubMed Web of Science ®Google Scholar
• You JS , JonesPA. Cancer genetics and epigenetics: two sides of the same coin?Cancer Cell22(1), 9–20 (2012).
   PubMed Web of Science ®Google Scholar
• Boice M , SalloumD , MourcinFet al. Loss of the HVEM tumor suppressor in lymphoma and restoration by modified CAR-T cells. Cell167(2), 405–418.e13 (2016).
   PubMed Web of Science ®Google Scholar
• Pasqualucci L . Molecular pathogenesis of germinal center-derived B cell lymphomas. Immunol. Rev.288(1), 240–261 (2019).
   PubMed Web of Science ®Google Scholar
• Green MR . Chromatin modifying gene mutations in follicular lymphoma. Blood131(6), 595–604 (2018).
   PubMed Web of Science ®Google Scholar
• Martignoles J-A , DelhommeauF , HirschP. Genetic hierarchy of acute myeloid leukemia: from clonal hematopoiesis to molecular residual disease. Int. J. Mol. Sci.19(12), 3850 (2018).
   PubMed Web of Science ®Google Scholar
• Jones PA , LairdPW. Cancer-epigenetics comes of age. Nat. Genet.21(2), 163–167 (1999).
   PubMed Web of Science ®Google Scholar
• Jones PA , BaylinSB. The epigenomics of cancer. Cell128(4), 683–692 (2007).
   PubMed Web of Science ®Google Scholar
• Park W-Y , HongB-J , LeeJ , ChoiC , KimM-Y. H3K27 demethylase JMJD3 Employs the NF-κB and BMP signaling pathways to modulate the tumor microenvironment and promote melanoma progression and metastasis. Cancer Res.76(1), 161–170 (2016).
   PubMed Web of Science ®Google Scholar
• Hanahan D , CoussensLM. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell21(3), 309–322 (2012).
   PubMed Web of Science ®Google Scholar
• Hirata E , SahaiE. Tumor microenvironment and differential responses to therapy. Cold Spring Harb. Perspect. Med.7(7), a026781 (2017).
   PubMed Web of Science ®Google Scholar
• Senthebane DA , JonkerT , RoweAet al. The role of tumor microenvironment in chemoresistance: 3d extracellular matrices as accomplices. Int. J. Mol. Sci. Page 385019(10), 2861 (2018).
   PubMed Web of Science ®Google Scholar
• Senthebane DA , RoweA , ThomfordNEet al. The role of tumor microenvironment in chemoresistance: to survive, keep your enemies closer. Int. J. Mol. Sci. Page 3850. 18(7), 1586 (2017).
   PubMed Web of Science ®Google Scholar
• Guilloton F , CaronG , MénardCet al. Mesenchymal stromal cells orchestrate follicular lymphoma cell niche through the CCL2-dependent recruitment and polarization of monocytes. Blood119(11), 2556–2567 (2012).
   PubMed Web of Science ®Google Scholar
• Zhou J , DingT , PanW , ZhuLY , LiL , ZhengL. Increased intratumoral regulatory T cells are related to intratumoral macrophages and poor prognosis in hepatocellular carcinoma patients. Int. J. Cancer125(7), 1640–1648 (2009).
   PubMed Web of Science ®Google Scholar
• Mamrot J , BalachandranS , SteeleEJ , LindleyRA. Molecular model linking Th2 polarized M2 tumour-associated macrophages with deaminase-mediated cancer progression mutation signatures. Scand. J. Immunol.89(5), e12760 (2019).
   PubMed Web of Science ®Google Scholar
• Wang D , YangL , YueDet al. Macrophage-derived CCL22 promotes an immunosuppressive tumor microenvironment via IL-8 in malignant pleural effusion. Cancer Lett.452, 244–253 (2019).
   PubMed Web of Science ®Google Scholar
• Mariathasan S , TurleySJ , NicklesDet al. TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature554(7693), 544–548 (2018).
   PubMed Web of Science ®Google Scholar
• Kather JN , Suarez-CarmonaM , CharoentongPet al. Topography of cancer-associated immune cells in human solid tumors. Elife7, 16878 (2018).
   Web of Science ®Google Scholar
• Terranova-Barberio M , ThomasS , MunsterPN. Epigenetic modifiers in immunotherapy: a focus on checkpoint inhibitors. Immunotherapy8(6), 705–719 (2016).
   PubMed Web of Science ®Google Scholar
• Jones PA , OhtaniH , ChakravarthyA , DeCarvalho DD. Epigenetic therapy in immune-oncology. Nat. Rev. Cancer22, 1 (2019).
   Google Scholar
• Toor SM , SasidharanNair V , DecockJ , ElkordE. Immune checkpoints in the tumor microenvironment. Semin. Cancer Biol.19 (2019). S1044-579X(19)30123-3
   Google Scholar
• Costa A , Scholer-DahirelA , Mechta-GrigoriouF. The role of reactive oxygen species and metabolism on cancer cells and their microenvironment. Semin. Cancer Biol.25, 23–32 (2014).
   PubMed Web of Science ®Google Scholar
• Monteran L , ErezN. The dark side of fibroblasts: cancer-associated fibroblasts as mediators of immunosuppression in the tumor microenvironment. Front. Immunol.10, 1835 (2019).
   PubMed Web of Science ®Google Scholar
• Givel A-M , KiefferY , Scholer-DahirelAet al. miR200-regulated CXCL12β promotes fibroblast heterogeneity and immunosuppression in ovarian cancers. Nat. Commun.9(1), 1056 (2018).
   PubMedGoogle Scholar
• Costa A , KiefferY , Scholer-DahirelAet al. Fibroblast heterogeneity and immunosuppressive environment in human breast cancer. Cancer Cell33(3), 463–479.e10 (2018).
   PubMed Web of Science ®Google Scholar
• Chakravarthy A , KhanL , BenslerNP , BoseP , DeCarvalho DD. TGF-β-associated extracellular matrix genes link cancer-associated fibroblasts to immune evasion and immunotherapy failure. Nat. Commun.9(1), 4692 (2018).
   PubMed Web of Science ®Google Scholar
• Madar S , GoldsteinI , RotterV. “Cancer associated fibroblasts” – more than meets the eye. Trends Mol. Med.19(8), 447–453 (2013).
   PubMed Web of Science ®Google Scholar
• Chang JE , TurleySJ. Stromal infrastructure of the lymph node and coordination of immunity. Trends Immunol.36(1), 30–39 (2015).
   PubMed Web of Science ®Google Scholar
• Colbeck EJ , AgerA , GallimoreA , JonesGW. Tertiary lymphoid structures in cancer: drivers of antitumor immunity, immunosuppression, or bystander sentinels in disease?Front. Immunol.8, 867 (2017).
   PubMed Web of Science ®Google Scholar
• Bindea G , MlecnikB , TosoliniMet al. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity39(4), 782–795 (2013).
   PubMed Web of Science ®Google Scholar
• Riedel A , ShorthouseD , HaasL , HallBA , ShieldsJ. Tumor-induced stromal reprogramming drives lymph node transformation. Nat. Immunol.17(9), 1118–1127 (2016).
   PubMed Web of Science ®Google Scholar
• Pandey S , MourcinF , MarchandTet al. IL-4/CXCL12 loop is a key regulator of lymphoid stroma function in follicular lymphoma. Blood129(18), 2507–2518 (2017).
   PubMed Web of Science ®Google Scholar
• Grégoire M , GuillotonF , PangaultCet al. Neutrophils trigger a NF-κB dependent polarization of tumor-supportive stromal cells in germinal center B-cell lymphomas. Oncotarget6(18), 16471–16487 (2015).
   PubMedGoogle Scholar
• Mathot P , GrandinM , DevaillyGet al. DNA methylation signal has a major role in the response of human breast cancer cells to the microenvironment. Oncogenesis6(10), e390 (2017).
   PubMedGoogle Scholar
• Le Jiang , GondaTA , GambleMVet al. Global Hypomethylation of genomic DNA in cancer-associated myofibroblasts. Cancer Res.68(23), 9900–9908 (2008).
   PubMed Web of Science ®Google Scholar
• Ling E , RingelA , Sigal-BatikoffIet al. Human colorectal cancer stage-dependent global DNA hypomethylation of cancer-associated fibroblasts. Anticancer Res.36(9), 4503–4507 (2016).
   PubMed Web of Science ®Google Scholar
• Vizoso M , PuigM , CarmonaFJet al. Aberrant DNA methylation in non-small cell lung cancer-associated fibroblasts. Carcinogenesis36(12), 1453–1463 (2015).
   PubMed Web of Science ®Google Scholar
• Zeisberg EM , ZeisbergM. The role of promoter hypermethylation in fibroblast activation and fibrogenesis. J. Pathol.229(2), 264–273 (2013).
   PubMed Web of Science ®Google Scholar
• Albrengues J , BerteroT , GrassetEet al. Epigenetic switch drives the conversion of fibroblasts into proinvasive cancer-associated fibroblasts. Nat. Commun.6(1), 10204 (2015).
   PubMedGoogle Scholar
• Bechtel W , McGoohanS , ZeisbergEMet al. Methylation determines fibroblast activation and fibrogenesis in the kidney. Nat. Med.16(5), 544–550 (2010).
   PubMed Web of Science ®Google Scholar
• Mishra R , HaldarS , PlacencioVet al. Stromal epigenetic alterations drive metabolic and neuroendocrine prostate cancer reprogramming. J. Clin. Invest.128(10), 4472–4484 (2018).
   PubMed Web of Science ®Google Scholar
• Al-Kharashi LA , Al-MohannaFH , TulbahA , AboussekhraA. The DNA methyl-transferase protein DNMT1 enhances tumor-promoting properties of breast stromal fibroblasts. Oncotarget9(2), 2329–2343 (2018).
   PubMedGoogle Scholar
• Li A , ChenP , LengY , KangJ. Histone deacetylase 6 regulates the immunosuppressive properties of cancer-associated fibroblasts in breast cancer through the STAT3-COX2-dependent pathway. Oncogene37(45), 5952–5966 (2018).
   PubMed Web of Science ®Google Scholar
• Garcia-Gomez A , Rodríguez-UbrevaJ , BallestarE. Epigenetic interplay between immune, stromal and cancer cells in the tumor microenvironment. Clin. Immunol.196, 64–71 (2018).
   PubMed Web of Science ®Google Scholar
• Kim DJ , DunleaveyJM , XiaoLet al. Suppression of TGFβ-mediated conversion of endothelial cells and fibroblasts into cancer associated (myo)fibroblasts via HDAC inhibition. Br. J. Cancer118(10), 1359–1368 (2018).
   PubMed Web of Science ®Google Scholar
• Kumar V , DonthireddyL , MarvelDet al. Cancer-associated fibroblasts neutralize the anti-tumor effect of CSF1 receptor blockade by inducing PMN-MDSC infiltration of tumors. Cancer Cell32(5), 654–668.e5 (2017).
   PubMed Web of Science ®Google Scholar
• Kim DE , ProcopioM-G , GhoshSet al. Convergent roles of ATF3 and CSL in chromatin control of cancer-associated fibroblast activation. J. Exp. Med.214(8), 2349–2368 (2017).
   PubMed Web of Science ®Google Scholar
• Maeda M , TakeshimaH , IidaNet al. Cancer cell niche factors secreted from cancer-associated fibroblast by loss of H3K27me3. Gut gutjnl–2018–317645 (2019).
   PubMed Web of Science ®Google Scholar
• Zong Y , HuangJ , SankarasharmaDet al. Stromal epigenetic dysregulation is sufficient to initiate mouse prostate cancer via paracrine Wnt signaling. Proc. Natl Acad. Sci. USA109(50), E3395–3404 (2012).
   PubMed Web of Science ®Google Scholar
• Xu L , DengQ , PanYet al. Cancer-associated fibroblasts enhance the migration ability of ovarian cancer cells by increasing EZH2 expression. Int. J. Mol. Med.33(1), 91–96 (2014).
   PubMed Web of Science ®Google Scholar
• Kaukonen R , MaiA , GeorgiadouMet al. Normal stroma suppresses cancer cell proliferation via mechanosensitive regulation of JMJD1a-mediated transcription. Nat. Commun.7(1), 12237 (2016).
   PubMedGoogle Scholar
• Schoepp M , StröseAJ , HaierJ. Dysregulation of miRNA expression in cancer associated fibroblasts (CAFs) and its consequences on the tumor microenvironment. Cancers (Basel)9(6), 54 (2017).
   PubMed Web of Science ®Google Scholar
• Musumeci M , CoppolaV , AddarioAet al. Control of tumor and microenvironment cross-talk by miR-15a and miR-16 in prostate cancer. Oncogene30(41), 4231–4242 (2011).
   PubMed Web of Science ®Google Scholar
• Josson S , GururajanM , SungSYet al. Stromal fibroblast-derived miR-409 promotes epithelial-to-mesenchymal transition and prostate tumorigenesis. Oncogene34(21), 2690–2699 (2015).
   PubMed Web of Science ®Google Scholar
• Batista L , BourachotB , MateescuB , ReyalF , Mechta-GrigoriouF. Regulation of miR-200c/141 expression by intergenic DNA-looping and transcriptional read-through. Nat. Commun.7(1), 8959 (2016).
   PubMedGoogle Scholar
• Togashi Y , ShitaraK , NishikawaH. Regulatory T cells in cancer immunosuppression – implications for anticancer therapy. Nat. Rev. Clin. Oncol.16, 356–371 (2019).
   PubMed Web of Science ®Google Scholar
• Safari E , GhorghanluS , Ahmadi-KhiaviH , MehranfarS , RezaeiR , MotallebnezhadM. Myeloid-derived suppressor cells and tumor: current knowledge and future perspectives. J. Cell. Physiol.117(1), 7021 (2018).
   Google Scholar
• Zhang C , WangS , LiuY , YangC. Epigenetics in myeloid derived suppressor cells: a sheathed sword towards cancer. Oncotarget7(35), 57452–57463 (2016).
   PubMedGoogle Scholar
• Heine A , HeldSAE , Schulte-SchreppingJet al. Generation and functional characterization of MDSC-like cells. Oncoimmunology6(4), e1295203 (2017).
   PubMed Web of Science ®Google Scholar
• Lal G , ZhangN , vander Touw Wet al. Epigenetic Regulation of Foxp3 Expression in Regulatory T Cells by DNA Methylation. J. Immunol.182(1), 259–273 (2009).
   PubMed Web of Science ®Google Scholar
• Rodríguez-Ubreva J , Català-MollF , ObermajerNet al. Prostaglandin E2 leads to the acquisition of DNMT3A-dependent tolerogenic functions in human myeloid-derived suppressor cells. Cell Rep.21(1), 154–167 (2017).
   PubMed Web of Science ®Google Scholar
• Sido JM , YangX , NagarkattiPS , NagarkattiM. Δ9-Tetrahydrocannabinol-mediated epigenetic modifications elicit myeloid-derived suppressor cell activation via STAT3/S100A8. J. Leukoc. Biol.97(4), 677–688 (2015).
   PubMed Web of Science ®Google Scholar
• Sido JM , NagarkattiPS , NagarkattiM. Δ9-Tetrahydrocannabinol attenuates allogeneic host-versus-graft response and delays skin graft rejection through activation of cannabinoid receptor 1 and induction of myeloid-derived suppressor cells. J. Leukoc. Biol.98(3), 435–447 (2015).
   PubMed Web of Science ®Google Scholar
• Sahakian E , PowersJJ , ChenJet al. Histone deacetylase 11: a novel epigenetic regulator of myeloid derived suppressor cell expansion and function. Mol. Immunol.63(2), 579–585 (2015).
   PubMed Web of Science ®Google Scholar
• Youn J-I , KumarV , CollazoMet al. Epigenetic silencing of retinoblastoma gene regulates pathologic differentiation of myeloid cells in cancer. Nat. Immunol.14(3), 211–220 (2013).
   PubMed Web of Science ®Google Scholar
• Redd PS , IbrahimML , KlementJDet al. SETD1B Activates iNOS Expression in Myeloid-Derived Suppressor Cells. Cancer Res.77(11), 2834–2843 (2017).
   PubMed Web of Science ®Google Scholar
• Peng D , KryczekI , NagarshethNet al. Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy. Nature527(7577), 249–253 (2015).
   PubMed Web of Science ®Google Scholar
• Nagarsheth N , PengD , KryczekIet al. PRC2 epigenetically silences Th1-Type chemokines to suppress effector T-Cell trafficking in colon cancer. Cancer Res.76(2), 275–282 (2016).
   PubMed Web of Science ®Google Scholar
• Guo X , QiuW , WangJet al. Glioma exosomes mediate the expansion and function of myeloid-derived suppressor cells through microRNA-29a/Hbp1 and microRNA-92a/Prkar1a pathways. Int. J. Cancer144, 3111–3126 ijc.32052 (2018).
   Web of Science ®Google Scholar
• Guo X , QiuW , LiuQet al. Immunosuppressive effects of hypoxia-induced glioma exosomes through myeloid-derived suppressor cells via the miR-10a/ Rora and miR-21/ Pten Pathways. Oncogene37(31), 4239–4259 (2018).
   PubMed Web of Science ®Google Scholar
• Huber V , VallacchiV , FlemingVet al. Tumor-derived microRNAs induce myeloid suppressor cells and predict immunotherapy resistance in melanoma. J. Clin. Invest.128(12), 5505–5516 (2018).
   PubMed Web of Science ®Google Scholar
• Zhou J , LiX , WuXet al. Exosomes released from tumor-associated macrophages transfer miRNAs that induce a Treg/Th17 cell imbalance in epithelial ovarian cancer. Cancer Immunol. Res.6(12), 1578–1592 (2018).
   PubMed Web of Science ®Google Scholar
• Yoo CB , JonesPA. Epigenetic therapy of cancer: past, present and future. Nat. Rev. Drug Discov.5(1), 37–50 (2006).
   PubMed Web of Science ®Google Scholar
• Gherardini L , SharmaA , CapobiancoE , CintiC. Targeting cancer with Epi-drugs: a precision medicine perspective. Curr. Pharm. Biotechnol.17(10), 856–865 (2016).
   PubMed Web of Science ®Google Scholar
• Roulois D , LooYau H , SinghaniaRet al. DNA-demethylating agents target colorectal cancer cells by inducing viral mimicry by endogenous transcripts. Cell162(5), 961–973 (2015).
   PubMed Web of Science ®Google Scholar
• Chiappinelli KB , StrisselPL , DesrichardAet al. Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses. Cell162(5), 974–986 (2015).
   PubMed Web of Science ®Google Scholar
• Goswami S , ApostolouI , ZhangJet al. Modulation of EZH2 expression in T cells improves efficacy of anti-CTLA-4 therapy. J. Clin. Invest.128(9), 3813–3818 (2018).
   PubMed Web of Science ®Google Scholar
• Stone ML , ChiappinelliKB , LiHet al. Epigenetic therapy activates type I interferon signaling in murine ovarian cancer to reduce immunosuppression and tumor burden. Proc. Natl Acad. Sci. USA114(51), E10981–E10990 (2017).
   PubMed Web of Science ®Google Scholar
• Christmas BJ , RafieCI , HopkinsACet al. Entinostat converts immune-resistant breast and pancreatic cancers into checkpoint-responsive tumors by reprogramming tumor-infiltrating MDSCs. Cancer Immunol. Res.6(12), 1561–1577 (2018).
   PubMed Web of Science ®Google Scholar
• Briere D , SudhakarN , WoodsDMet al. The class I/IV HDAC inhibitor mocetinostat increases tumor antigen presentation, decreases immune suppressive cell types and augments checkpoint inhibitor therapy. Cancer Immunol. Immunother.67(3), 381–392 (2018).
   PubMed Web of Science ®Google Scholar
• Yamamoto K , TateishiK , KudoYet al. Stromal remodeling by the BET bromodomain inhibitor JQ1 suppresses the progression of human pancreatic cancer. Oncotarget7(38), 61469–61484 (2016).
   PubMedGoogle Scholar
• Issa J-PJ , KantarjianHM. Targeting DNA methylation. Clin. Cancer Res.15(12), 3938–3946 (2009).
   PubMed Web of Science ®Google Scholar
• Zhao H , NingS , NolleyRet al. The immunomodulatory anticancer agent, RRx-001, induces an interferon response through epigenetic induction of viral mimicry. Clin. Epigenetics9(1), 4 (2017).
   PubMedGoogle Scholar
• Ghoneim HE , FanY , MoustakiAet al. De novo epigenetic programs inhibit PD-1 blockade-mediated T Cell rejuvenation. Cell170(1), 142–157.e19 (2017).
   PubMed Web of Science ®Google Scholar
• Terracina KP , GrahamLJ , PayneKKet al. DNA methyltransferase inhibition increases efficacy of adoptive cellular immunotherapy of murine breast cancer. Cancer Immunol. Immunother.65(9), 1061–1073 (2016).
   PubMed Web of Science ®Google Scholar
• Mikyšková R , IndrováM , VlkováVet al. DNA demethylating agent 5-azacytidine inhibits myeloid-derived suppressor cells induced by tumor growth and cyclophosphamide treatment. J. Leukoc. Biol.95(5), 743–753 (2014).
   PubMed Web of Science ®Google Scholar
• Sala L , Franco-VallsH , StanisavljevicJet al. Abrogation of myofibroblast activities in metastasis and fibrosis by methyltransferase inhibition. Int. J. Cancer19, 1423 (2019).
   Google Scholar
• Lee S , KimH-S , RohK-Het al. DNA methyltransferase inhibition accelerates the immunomodulation and migration of human mesenchymal stem cells. Sci. Rep.5, 8020 (2015).
   PubMed Web of Science ®Google Scholar
• Huang S , WangZ , ZhouJet al. EZH2 inhibitor GSK126 suppresses anti-tumor immunity by driving production of myeloid-derived suppressor cells. Cancer Res.79, 2009–2020 (2019).
   PubMed Web of Science ®Google Scholar
• Rosborough BR , CastellanetaA , NatarajanS , ThomsonAW , TurnquistHR. Histone deacetylase inhibition facilitates GM-CSF-mediated expansion of myeloid-derived suppressor cells in vitro and in vivo. J. Leukoc. Biol.91(5), 701–709 (2012).
   PubMed Web of Science ®Google Scholar
• Reddy P . Editorial: HDAC inhibition begets more MDSCs. J. Leukoc. Biol.91(5), 679–681 (2012).
   PubMed Web of Science ®Google Scholar
• Tao R , de ZoetenEF , OzkaynakEet al. Deacetylase inhibition promotes the generation and function of regulatory T cells. Nat. Med.13(11), 1299–1307 (2007).
   PubMed Web of Science ®Google Scholar
• Doñas C , FritzM , ManríquezVet al. Trichostatin A promotes the generation and suppressive functions of regulatory T cells. Clin. Dev. Immunol.2013(67), 679804–679808 (2013).
   PubMedGoogle Scholar
• Akimova T , GeG , GolovinaTet al. Histone/protein deacetylase inhibitors increase suppressive functions of human FOXP3+ Tregs. Clin. Immunol.136(3), 348–363 (2010).
   PubMed Web of Science ®Google Scholar
• Nguyen AH , ElliottIA , WuNet al. Histone deacetylase inhibitors provoke a tumor supportive phenotype in pancreatic cancer associated fibroblasts. Oncotarget8(12), 19074–19088 (2017).
   PubMedGoogle Scholar
• Pazolli E , AlspachE , MilczarekA , PriorJ , Piwnica-WormsD , StewartSA. Chromatin remodeling underlies the senescence-associated secretory phenotype of tumor stromal fibroblasts that supports cancer progression. Cancer Res.72(9), 2251–2261 (2012).
   PubMed Web of Science ®Google Scholar
• Cramer SA , AdjeiIM , LabhasetwarV. Advancements in the delivery of epigenetic drugs. Expert Opin. Drug Deliv.12(9), 1501–1512 (2015).
   PubMed Web of Science ®Google Scholar
• Zhu Y , YuF , TanY , YuanH , HuF. Strategies of targeting pathological stroma for enhanced antitumor therapies. Pharmacol. Res.148, 104401 (2019).
   PubMed Web of Science ®Google Scholar
• Schwartzman O , TanayA. Single-cell epigenomics: techniques and emerging applications. Nat. Rev. Genet.16(12), 716–726 (2015).
   PubMed Web of Science ®Google Scholar
• Lee D-S , LuoC , ZhouJet al. Simultaneous profiling of 3D genome structure and DNA methylation in single human cells. Nat. Methods62(10), 1–8 (2019).
   Google Scholar
• Kelsey G , StegleO , ReikW. Single-cell epigenomics: recording the past and predicting the future. Science358(6359), 69–75 (2017).
   PubMed Web of Science ®Google Scholar