TIM-3 + CD8 T cells with a terminally exhausted phenotype retain functional capacity in hematological malignancies

• DOI: 10.1126/sciimmunol.adg1094
• Publication Date: 2024-04-19T17:58:10Z
• Authors: Simone A. Minnie; Olivia G. Waltner; Ping Zhang; Shuichiro Takahashi; Nicole S. Nemyche...; Kathleen S. Ensbey; Christine R. 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
• Keywords: 0301 basic medicine; 03 medical and health sciences; Phenotype; Hematologic Neoplasms; Tumor Microenvironment; Humans; CD8-Positive T-Lymphocytes; Multiple Myeloma; Hepatitis A Virus Cellular Receptor 2

Chronic antigen stimulation is thought to generate dysfunctional CD8 T cells. Here, we identify a 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 DNA accessibility revealed that genes encoding these functional proteins correlated with BATF motif accessibility. IFN-γ + effectively killed myeloma comparable efficacy transitory effectors, disease progression numerical deficits . We also observed within CD19-targeted chimeric receptor cells, which CD19 leukemia An signature was recapitulated EX cells from human cancers, including lymphoma. characterize hematological malignancies paradoxically retains function distinct found chronic viral infections. Thus, represent potential target for immunotherapy of blood cancers.