GSE262306 TIM-3 + CD8 T cells with a terminally exhausted phenotype retain functional capacity in hematological malignancies

Contributors : Simone Minnie ; Olivia Waltner ; Geoffrey Hill ; Scott FurlanSeries Type : Expression profiling by high throughput sequencing ; OtherOrganism : Mus musculusChronic 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 (TPHEX), 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. IFNγ+ TPHEX effectively killed myeloma with comparable efficacy to transitory effectors, and disease progression correlated with numer ical deficits in IFNγ+ TPHEX. We also observed IFNγ+ TPHEX within CD19-targeted chimeric antigen receptor T cells, which killed CD19+ leukemia cells. Importantly, an IFNγ+ TPHEX gene signature was recapitulated in TEX cells from human cancers, including myeloma and lymphoma. Here we characterize a TEX subset in hematological malignancies that paradoxically retains function and is distinct from dysfunctional TEX found in chronic viral infections. Thus, IFNγ+ TPHEX represent a potential target for immunotherapy of blood cancers.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Other Mus musculus Source Type: research