Natural Killer Cells Suppress T Cell-Associated Tumor Immune Evasion
| Autor: | Kelly M Ramsbottom, Conor J. Kearney, Stephin J. Vervoort, Lizzy Pijpers, Jessica Michie, Jane Oliaro, Ricky W. Johnstone, Madison J. Kelly, Andrew J. Freeman |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Cytotoxicity
Immunologic Male 0301 basic medicine T-Lymphocytes T cell medicine.medical_treatment Transplantation Heterologous Antigen presentation Major histocompatibility complex General Biochemistry Genetics and Molecular Biology Natural killer cell Interferon-gamma Mice 03 medical and health sciences 0302 clinical medicine Interferon Cell Line Tumor MHC class I medicine Animals Humans Melanoma lcsh:QH301-705.5 Mice Knockout Antigen Presentation biology Perforin Histocompatibility Antigens Class I Janus Kinase 1 Immunotherapy Coculture Techniques Killer Cells Natural Mice Inbred C57BL Gene Ontology 030104 developmental biology medicine.anatomical_structure Cell killing lcsh:Biology (General) Cancer research biology.protein Female Tumor Escape CRISPR-Cas Systems 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Cell Reports, Vol 28, Iss 11, Pp 2784-2794.e5 (2019) |
| ISSN: | 2211-1247 |
| Popis: | Summary: Despite the clinical success of cancer immunotherapies, the majority of patients fail to respond or develop resistance through disruption of pathways that promote neo-antigen presentation on MHC I molecules. Here, we conducted a series of unbiased, genome-wide CRISPR/Cas9 screens to identify genes that limit natural killer (NK) cell anti-tumor activity. We identified that genes associated with antigen presentation and/or interferon-γ (IFN-γ) signaling protect tumor cells from NK cell killing. Indeed, Jak1-deficient melanoma cells were sensitized to NK cell killing through attenuated NK cell-derived IFN-γ-driven transcriptional events that regulate MHC I expression. Importantly, tumor cells that became resistant to T cell killing through enrichment of MHC I-deficient clones were highly sensitive to NK cell killing. Taken together, we reveal the genes targeted by tumor cells to drive checkpoint blockade resistance but simultaneously increase their vulnerability to NK cells, unveiling NK cell-based immunotherapies as a strategy to antagonize tumor immune escape. : Freeman et al. use a series of genome-wide loss-of-function genetic screens to identify genes that limit tumor sensitivity to killing by natural killer cells. The findings highlight that natural killer cells can suppress tumor immune evasion from T cells, identifying a potential strategy to overcome resistance to checkpoint blockade therapy. Keywords: natural killer cell, CRISPR screening, tumor immune evasion, immunotherapy |
| Databáze: | OpenAIRE |
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