作者
Myrna R Nahas, Dina Stroopinsky, Jacalyn Rosenblatt, Leandra Cole, Athalia R Pyzer, Eleni Anastasiadou, Anna Sergeeva, Adam Ephraim, Abigail Washington, Shira Orr, Malgorzata McMasters, Matthew Weinstock, Salvia Jain, Rebecca K Leaf, Haider Ghiasuddin, Maryam Rahimian, Jessica Liegel, Jeffrey J Molldrem, Frank Slack, Donald Kufe, David Avigan
发表日期
2019/5
期刊
British journal of haematology
卷号
185
期号
4
页码范围
679-690
简介
Acute myeloid leukaemia (AML) is a lethal haematological malignancy characterized by an immunosuppressive milieu in the tumour microenvironment (TME) that fosters disease growth and therapeutic resistance. Hypomethylating agents (HMAs) demonstrate clinical efficacy in AML patients and exert immunomodulatory activities. In the present study, we show that guadecitabine augments both antigen processing and presentation, resulting in increased AML susceptibility to T cell‐mediated killing. Exposure to HMA results in the activation of the endogenous retroviral pathway with concomitant downstream amplification of critical mediators of inflammation. In an immunocompetent murine leukaemia model, guadecitabine negatively regulates inhibitory accessory cells in the TME by decreasing PD‐1 (also termed PDCD1) expressing T cells and reducing AML‐mediated expansion of myeloid‐derived suppressor …
学术搜索中的文章
MR Nahas, D Stroopinsky, J Rosenblatt, L Cole… - British journal of haematology, 2019