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PRDM1 is a key regulator of the natural killer T-cell central memory program and effector function.
Cancer Immunol Res
January 2025
Baylor College of Medicine, Houston, TX, United States.
Natural killer T cells (NKTs) are a promising platform for cancer immunotherapy, but few genes involved in regulation of NKT therapeutic activity have been identified. To find regulators of NKT functional fitness, we developed a CRISPR/Cas9-based mutagenesis screen that employs a guide RNA (gRNA) library targeting 1,118 immune-related genes. Unmodified NKTs and NKTs expressing a GD2-specific chimeric antigen receptor (GD2.
View Article and Find Full Text PDFSingle-cell profiling transcriptomic reveals cellular heterogeneity and cellular crosstalk in breast cancer lymphatic node, bone, and brain metastases.
Sci Rep
January 2025
Department of Radiotherapy Oncology, The Fourth Hospital of Hebei Medical University, No. 169, Tianshan Street, Hebei, Shijiazhuang, 050035, Hebei Province, China.
Breast cancer is the most common malignant tumor in the world, and its metastasis is the main cause of death in breast cancer patients. However, the differences between primary breast cancer tissue and lymphatic node, bone, and brain metastases at the single-cell level are not fully understood. We analyzed the microenvironment heterogeneity in samples of primary breast cancer (n = 4), breast cancer lymphatic node metastasis (n = 4), breast cancer brain metastasis (n = 3), and breast cancer bone metastasis (n = 2) using single-cell sequencing data from the GEO database.
View Article and Find Full Text PDFCell type-specific upregulation of NKG2D ligand MICA in response to APTO253.
Ann Transl Med
December 2024
Institute for Tumor Immunology, Center for Tumor Biology and Immunology, Philipps-University Marburg, Marburg, Germany.
One of the most important targets for natural killer (NK) cell-mediated therapy is the induction of natural killer group 2D ligand (NKG2D-L) expression. APTO253 is a small molecule that selectively kills acute myeloid leukemia (AML) cells, and it has been reported that APTO253 can induce Krüppel-like factor 4 (KLF4) expression and downregulate c-MYC expression. Recently, we discovered a novel role of APTO253 in modulating the NK cell response by inducing surface expression of NKG2D-Ls, especially MHC class I polypeptide-related sequence A (MICA), in AML cells.
View Article and Find Full Text PDFSMARCA4 regulates the NK-mediated killing of senescent cells.
Sci Adv
January 2025
MRC Laboratory of Medical Sciences (LMS), Du Cane Road, London W12 0NN, UK.
Induction of senescence by chemotherapeutic agents arrests cancer cells and activates immune surveillance responses to contribute to therapy outcomes. In this investigation, we searched for ways to enhance the NK-mediated elimination of senescent cells. We used a staggered screen approach, first identifying siRNAs potentiating the secretion of immunomodulatory cytokines to later test for their ability to enhance NK-mediated killing of senescent cells.
View Article and Find Full Text PDFScreening of necroptosis-related genes and evaluating the prognostic capacity, clinical value, and the effect of their copy number variations in acute myeloid leukemia.
BMC Cancer
January 2025
The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi Children's Hospital, Wuxi, 214023, China.
Background: Acute myeloid leukemia (AML) is an aggressive hematological neoplasm. Little improvement in survival rates has been achieved over the past few decades. Necroptosis has relationship with certain types of malignancies outcomes.
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