9 research outputs found
T-BET and EOMES sustain mature human NK cell identity and antitumor function
Since the T-box transcription factors (TFs) T-BET and EOMES are necessary for initiation of NK cell development, their ongoing requirement for mature NK cell homeostasis, function, and molecular programming remains unclear. To address this, T-BET and EOMES were deleted in unexpanded primary human NK cells using CRISPR/Cas9. Deleting these TFs compromised in vivo antitumor response of human NK cells. Mechanistically, T-BET and EOMES were required for normal NK cell proliferation and persistence in vivo. NK cells lacking T-BET and EOMES also exhibited defective responses to cytokine stimulation. Single-cell RNA-Seq revealed a specific T-box transcriptional program in human NK cells, which was rapidly lost following T-BET and EOMES deletion. Further, T-BET- and EOMES-deleted CD56bright NK cells acquired an innate lymphoid cell precursor-like (ILCP-like) profile with increased expression of the ILC-3-associated TFs RORC and AHR, revealing a role for T-box TFs in maintaining mature NK cell phenotypes and an unexpected role of suppressing alternative ILC lineages. Our study reveals the critical importance of sustained EOMES and T-BET expression to orchestrate mature NK cell function and identity
Supplementary Figure S7 from Memory-like Differentiation, Tumor-Targeting mAbs, and Chimeric Antigen Receptors Enhance Natural Killer Cell Responses to Head and Neck Cancer
Supplementary Figure 7. EphA2-CAR-ML NK cells require intracellular CAR signaling and have antigen specific enhanced response to HNSCC.</p
Supplementary Figure S1 from Memory-like Differentiation, Tumor-Targeting mAbs, and Chimeric Antigen Receptors Enhance Natural Killer Cell Responses to Head and Neck Cancer
Supplementary Figure 1. Memory-Like (ML) NK cells from normal donors exhibit improved ability to control HNSCC cell lines compared to conventional NK (cNK) cells.</p
Supplementary Figure S4 from Memory-like Differentiation, Tumor-Targeting mAbs, and Chimeric Antigen Receptors Enhance Natural Killer Cell Responses to Head and Neck Cancer
Supplementary Figure 4. Cetuximab does not impair in vitro growth of HNSCC cells or cause toxicity to mice in NSG xenograft models.</p
Supplementary Figure S2 from Memory-like Differentiation, Tumor-Targeting mAbs, and Chimeric Antigen Receptors Enhance Natural Killer Cell Responses to Head and Neck Cancer
Supplementary Figure 2. HNSCC cell lines and patient samples express multiple inhibitory and activating surface ligands.</p
Supplementary Figure S6 from Memory-like Differentiation, Tumor-Targeting mAbs, and Chimeric Antigen Receptors Enhance Natural Killer Cell Responses to Head and Neck Cancer
Supplementary Figure 6. EphA2-CAR ML NK cells display enhanced functional responses against HPV positive and HPV negative HNSCC cell lines.</p
Supplementary Figure S3 from Memory-like Differentiation, Tumor-Targeting mAbs, and Chimeric Antigen Receptors Enhance Natural Killer Cell Responses to Head and Neck Cancer
Supplementary Figure 3. Individual blockade of DNAM-1, NKG2D and CD2 modestly impairs NK cell activity against HNSCC.</p
Supplementary Figure S5 from Memory-like Differentiation, Tumor-Targeting mAbs, and Chimeric Antigen Receptors Enhance Natural Killer Cell Responses to Head and Neck Cancer
Supplementary Figure 5. Expression of EphA2 on target cells and gating strategy for CAR-expressing NK cells</p
Supplementary Table S1 from Memory-like Differentiation, Tumor-Targeting mAbs, and Chimeric Antigen Receptors Enhance Natural Killer Cell Responses to Head and Neck Cancer
Supplementary Table S1. Demographic and clinical data of advanced head and neck squamous cell carcinoma patients. </p