Inhibition of a G9a/DNMT network triggers immune-mediated bladder cancer regression

Segovia, Carlos; José‐Eneriz, Edurne San; Munera-Maravilla, Ester; Martínez‐Fernández, Mónica; Gárate, Leire; Miranda, Estíbaliz; Vilas-Zornoza, Amaia; Lodewijk, Iris; Rubio, Carolina; Segrelles, Carmen; Valcárcel, Luis Vítores; Rabal, Obdulia; Casares, Noëlia; Bernardini, Alejandra; Suárez-Cabrera, Cristian; López-Calderón, Fernando; Fortes, Puri; Casado, José Antonio; Dueñas, Marta; Villacampa, Felipe; Lasarte, Juan José; Guerrero-Ramos, Félix; Velasco, Guillermo; Oyarzábal, Julen; Castellano, Daniel; Agirre, Xabier; Prósper, Felipe; Paramio, Jesús M.

doi:10.1038/s41591-019-0499-y

Cited by 138 publications

(127 citation statements)

References 41 publications

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“…Open access inhibitors, 129 130 oncolytic viruses 131 or HDAC inhibitors and other epigenetic regulators. [132][133][134] Irrespective of this possibility, the ability of RCD to drive adaptive immunity intimately depends on the antigenicity of dying cells with respect to the availability and the functional status of the mature TCR repertoire of the host.…”

Section: Sources Of Icd Antigenicitymentioning

confidence: 99%

Consensus guidelines for the definition, detection and interpretation of immunogenic cell death

Galluzzi

Vitale

Warren

et al. 2020

J Immunother Cancer

680

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Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death (ICD), discuss the key factors that dictate the ability of dying cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation.

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Section: Sources Of Icd Antigenicitymentioning

confidence: 99%

Consensus guidelines for the definition, detection and interpretation of immunogenic cell death

Galluzzi

Vitale

Warren

et al. 2020

J Immunother Cancer

680

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“…A summary of most recent studies addressing combination strategies between epigenetics and immune environment in BlCa is presented in Table 1 [54][55][56][57][58][59][60][61][62][63][64]. Some studies have focused on obtaining methylation-based biomarkers with predictive value, namely concerning response to BCG-therapy [55][56][57].…”

Section: Role Of Immunoepigenetics?mentioning

confidence: 99%

“…Recently, Segovia et al [63] further dissected the epigenetic regulation of immune response to cancer. In this work it was shown that EHMT2 (or G9a) expression associated with poor outcome in BlCa and that targeting both EHMT2 and DNA methyltransferase (DNMT) activity (inhibitor CM-272) significantly enhances antitumor effects, that is potentiated when combining with anti-PD-L1 agent.…”

Section: Role Of Immunoepigenetics?mentioning

confidence: 99%

Targeting the Immune system and Epigenetic Landscape of Urological Tumors

Lobo

Jerónimo

Henrique

2020

IJMS

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In the last years, we have witnessed remarkable advances in targeted therapies for cancer patients. There is a growing effort to either replace or reduce the dose of unspecific, systemic (chemo)therapies, given the associated short- and long-term side effects, by introducing more specific targeted therapies as single or combination agents. Due to the well-known implications of the immune system and epigenetic landscape in modulating cancer development, both have been explored as potential targets in several malignancies, including those affecting the genitourinary tract. As the immune system function is also epigenetically regulated, there is rationale for combining both strategies. However, this is still rather underexplored, namely in urological tumors. We aim to briefly review the use of immune therapies in prostate, kidney, bladder, and testicular cancer, and further describe studies providing supporting evidence on their combination with epigenetic-based therapies.

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“…Several studies have demonstrated that histone methylation plays a vital role in PASMCs and PAH [90][91][92]. Histone lysine methyltransferase G9a is a key enzyme for generating H3K9me2, which is an epigenetic mark of gene suppression [93]. BIX-01294, a specific inhibitor of G9a, inhibited the proliferation of fetal PASMCs and led to cell cycle arrest in the G1 phase by inducing p21 expression.…”

Section: Histone Methylation In Pulmonary Arterial Hypertensionmentioning

confidence: 99%

Histone methylation and vascular biology

Wei

Zhu

et al. 2020

Clin Epigenet

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The vasculature not only transports oxygenated blood, metabolites, and waste products but also serves as a conduit for hormonal communication between distant tissues. Therefore, it is important to maintain homeostasis within the vasculature. Recent studies have greatly expanded our understanding of the regulation of vasculature development and vascular-related diseases at the epigenetic level, including by protein posttranslational modifications, DNA methylation, and noncoding RNAs. Integrating epigenetic mechanisms into the pathophysiologic conceptualization of complex and multifactorial vascular-related diseases may provide promising therapeutic approaches. Several reviews have presented detailed discussions of epigenetic mechanisms not including histone methylation in vascular biology. In this review, we primarily discuss histone methylation in vascular development and maturity, and in vascular diseases.

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Inhibition of a G9a/DNMT network triggers immune-mediated bladder cancer regression

Cited by 138 publications

References 41 publications

Consensus guidelines for the definition, detection and interpretation of immunogenic cell death

Consensus guidelines for the definition, detection and interpretation of immunogenic cell death

Targeting the Immune system and Epigenetic Landscape of Urological Tumors

Histone methylation and vascular biology

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