ZNF683 (Hobit) Marks a CD8+ T Cell Population Associated with Anti-Tumor Immunity Following Anti-PD-1 Therapy for Richter Syndrome

Coordinated Immune Cell Networks in the Bone Marrow Microenvironment Define the Graft versus Leukemia Response with Adoptive Cellular Therapy

“…T cell C0 displayed high expression of CD8A and the transcription factor ZNF683/Hobit, which is increasingly recognized as a mediator of CD8+ T cell cytotoxicity and a marker of tissue resident-memory subsets (Figure S1L-M). 54,55 In addition, this cluster highly expressed various effector genes (GZMB, GZMH, GNLY, PRF1, B3GAT1; Figure S1L). The T cell cluster C40 was characterized by similar expression of CD8A and effector genes (GZMA, GZMB, GZMH, TBX21, GNLY, B3GAT1) but with lower expression of ZNF683 compared to C0 yet still higher than other T cell clusters.…”

“…Previously published scRNA-seq data 55,71,72,75 were obtained and subsetted to contain cells of interest (CD8 T cells and NK cells if available). Meta data including Normal/Malignant or HSCT status were merged with cluster names.…”

“…We thus designated this cluster as a CD8 ZNF683 Hi CTL/T EMRA population. 55,143,144 The remaining T cell populations were characterized as CD4 T PE (clusters 2: CCR7, TCF7, and IL7R ) 5 , CD4 naive (cluster 18: SELL, CCR7, IL7R ) CD8 exhausted (T EX ) (cluster 5: KLRG1, TIGIT, PDCD1, GZMK ), 145,146,147 CD8 T CM (cluster 25: CXCR4 ), 88,148 T proliferating (T PROLIF ) (cluster 21: MKI67 ), and CD8 effector memory (T EM ) (cluster 40: CCL5, GZMA, GZMH, TBX21, ID2 ), 149 CD8 activated (cluster 26: FAS, ENTPD1, IL2RA, TNFRSF4 ), 150 unconventional T cells (i.e. MAIT and ɣδ T cells, cluster 28: TRGV9 ).…”

Predicting patient outcomes after treatment with immune checkpoint blockade: A review of biomarkers derived from diverse data modalities

“… 16 melanoma and NSCLC TIDE score – Lemvigh et al. 18 AML ZNF683 expressed in CE8+ effector and memory T cells Helmink et al. 20 melanoma CD79B, CD1D, CCR6, LAT, SKAP1, CETP, EIF1AY, RBP8, PTGDS TLS-related genes Hugo et al.…”

“…Recently, the ZNF683 gene was found to regulate T cell cytotoxicity and activation and to be highly expressed in CD8 + effector/memory T cells based on single-cell RNA sequencing (scRNA-seq) data of Richter syndrome patients; this finding was further validated in melanoma and HNSCC. 18 In addition to T cells, tertiary lymphoid structures (TLSs), organized aggregates of immune cells that form in chronically inflamed environments, have been shown to correlate with clinical outcomes in NSCLC, colorectal cancer (CRC), melanoma, and breast cancer. 19 A nine-gene signature was used to describe the TLS phenotype of melanoma after anti-CTLA4 or anti-PD1 treatment, as patients with higher average expression of these nine genes have significantly longer survival than those with relatively lower expression 20 ( Figure 1 A and Table 1 ).…”