Hypoxia induces HIF1ä¼?dependent epigenetic vulnerability in triple negative breast cancer to confer immune effector dysfunction and resistance to anti-PD-1 immunotherapy was written by Ma, Shijun;Zhao, Yue;Lee, Wee Chyan;Ong, Li-Teng;Lee, Puay Leng;Jiang, Zemin;Oguz, Gokce;Niu, Zhitong;Liu, Min;Goh, Jian Yuan;Wang, Wenyu;Bustos, Matias A.;Ehmsen, Sidse;Ramasamy, Adaikalavan;Hoon, Dave S. B.;Ditzel, Henrik J.;Tan, Ern Yu;Chen, Qingfeng;Yu, Qiang. And the article was included in Nature Communications in 2022.Application of 1373423-53-0 The following contents are mentioned in the article:
The hypoxic tumor microenvironment has been implicated in immune escape, but the underlying mechanism remains elusive. Using an in vitro culture system modeling human T cell dysfunction and exhaustion in triple-neg. breast cancer (TNBC), we find that hypoxia suppresses immune effector gene expression, including in T and NK cells, resulting in immune effector cell dysfunction and resistance to immunotherapy. We demonstrate that hypoxia-induced factor 1ä¼?(HIF1ä¼? interaction with HDAC1 and concurrent PRC2 dependency causes chromatin remolding resulting in epigenetic suppression of effector genes and subsequent immune dysfunction. Targeting HIF1ä¼?and the associated epigenetic machinery can reverse the immune effector dysfunction and overcome resistance to PD-1 blockade, as demonstrated both in vitro and in vivo using syngeneic and humanized mice models. These findings identify a HIF1ä¼?mediated epigenetic mechanism in immune dysfunction and provide a potential strategy to overcome immune resistance in TNBC. This study involved multiple reactions and reactants, such as Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0Application of 1373423-53-0).
Ethyl 3-((6-(4,5-dihydro-1H-benzo[d]azepin-3(2H)-yl)-2-(pyridin-2-yl)pyrimidin-4-yl)amino)propanoate (cas: 1373423-53-0) belongs to pyrimidine derivatives. Pyrimidine is an aromatic heterocyclic organic compound similar to pyridine. Therapy for fungal infections is based mainly on four classes of antifungals: azoles, echinocandins, polyenes, and pyrimidine analogs.Application of 1373423-53-0
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia