Purpose Of Review: In recent years, the rules of engagement between natural killer (NK) cells and their targets have become better defined with the identification of an array of NK surface molecules, notably the killer immunoglobulin-like (KIR) receptors and their ligands on target cells through which signals of activation or suppression of NK function are mediated. After allogeneic stem cell transplantation (SCT), the opportunity for NK cell activation can occur both in human leucocyte antigen (HLA) matched and HLA mismatched pairs. Although less well explored in HLA identical transplants, many studies confirm the importance of NK KIR mismatching in the graft-versus-leukemia effect in haploidentical (haplo) SCT and this has stimulated recent research to better define the role of NK mismatching on transplant outcome. In this review, we describe recent progress in identifying favorable and unfavorable NK matching in SCT.
Recent Findings: Recent studies focus less on KIR-HLA mismatching and more on KIR genes as tools to predict alloreactivity via NK licensing and activating KIR.
Summary: Current results show that transplant outcomes could be improved by judicious selection of favorable donors.
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http://dx.doi.org/10.1097/MOH.0000000000000384 | DOI Listing |
Mol Ther Oncol
September 2024
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Hematopoietic stem cell transplantation (HSCT) is widely used to treat patients with life-threatening hematologic and immune system disorders. Current nontargeted chemo-/radiotherapy conditioning regimens cause tissue injury and induce an array of immediate and delayed adverse effects, limiting the application of this life-saving treatment. The growing demand to replace canonical conditioning regimens has led to the development of alternative approaches, such as antibody-drug conjugates, naked antibodies, and CAR T cells.
View Article and Find Full Text PDFCancer 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 PDFClin Exp Med
January 2025
Immunology Department, Leibniz Research Center for Working Environment and Human Factors at TU Dortmund (IfADo), Dortmund, Germany.
Adoptive cell therapy (ACT) using natural killer (NK) cells has emerged as a promising therapeutic strategy for acute myeloid leukemia (AML), addressing challenges such as chemotherapy resistance and high relapse rates. Over the years, clinical trials and studies have explored various sources of NK cells, including ex vivo expanded NK cell lines, CAR-NK cells, peripheral blood-derived NK cells, and umbilical cord blood-derived NK cells. These therapies have demonstrated varying degrees of therapeutic efficacy, ranging from transient anti-leukemia activity to sustained remission in select patient groups.
View Article and Find Full Text PDFSci 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 PDFPLoS One
January 2025
Department of Gastroenterological and Transplant Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Bloodstream infections (BSIs) are significant postoperative complications associated with high mortality rates after liver transplantation (LT). Natural killer (NK) cells, which are key components of the innate immune system, have demonstrated potential to combat both infections and cancer. The use of activated NK cells to mitigate post-LT infections, particularly BSIs, has attracted considerable interest.
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