Impaired Death Receptor Signaling in Leukemia Causes Antigen-Independent Resistance by Inducing CAR T-cell Dysfunction

白血病中死亡受体信号传导受损会诱导 CAR-T 细胞功能障碍,从而导致抗原非依赖性耐药性

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作者:Nathan Singh #, Yong Gu Lee #, Olga Shestova, Pranali Ravikumar, Katharina E Hayer, Seok Jae Hong, Xueqing Maggie Lu, Raymone Pajarillo, Sangya Agarwal, Shunichiro Kuramitsu, Elena J Orlando, Karen Thudium Mueller, Charly R Good, Shelley L Berger, Ophir Shalem, Matthew D Weitzman, Noelle V Frey, Sha

Significance

Resistance to CART19 is a significant barrier to efficacy in the treatment of B-cell malignancies. This work demonstrates that impaired death receptor signaling in tumor cells causes failed CART19 cytotoxicity and drives CART19 dysfunction, identifying a novel mechanism of antigen-independent resistance to CAR therapy.See related commentary by Green and Neelapu, p. 492.

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