表型
癌症研究
生物
CD8型
脾脏
免疫学
遗传学
基因
抗原
作者
Simone A. Minnie,Olivia Waltner,Ping Zhang,Shūichirō Takahashi,Nicole S. Nemychenkov,Kathleen S. Ensbey,Christine Schmidt,Samuel R.W. Legg,Melissa Comstock,Julie R. Boiko,Ethan Nelson,Shruti S. Bhise,Alec B. Wilkens,Motoko Koyama,Madhav V. Dhodapkar,Marta Chesi,Stanley R. Riddell,Damian J. Green,Andrew Spencer,Scott N. Furlan,Geoffrey R. Hill
出处
期刊:Science immunology
[American Association for the Advancement of Science (AAAS)]
日期:2024-04-19
卷期号:9 (94)
标识
DOI:10.1126/sciimmunol.adg1094
摘要
Chronic antigen stimulation is thought to generate dysfunctional CD8 T cells. Here, we identify a CD8 T cell subset in the bone marrow tumor microenvironment that, despite an apparent terminally exhausted phenotype (T PHEX ), expressed granzymes, perforin, and IFN-γ. Concurrent gene expression and DNA accessibility revealed that genes encoding these functional proteins correlated with BATF expression and motif accessibility. IFN-γ + T PHEX effectively killed myeloma with comparable efficacy to transitory effectors, and disease progression correlated with numerical deficits in IFN-γ + T PHEX . We also observed IFN-γ + T PHEX within CD19-targeted chimeric antigen receptor T cells, which killed CD19 + leukemia cells. An IFN-γ + T PHEX gene signature was recapitulated in T EX cells from human cancers, including myeloma and lymphoma. Here, we characterize a T EX subset in hematological malignancies that paradoxically retains function and is distinct from dysfunctional T EX found in chronic viral infections. Thus, IFN-γ + T PHEX represent a potential target for immunotherapy of blood cancers.
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