Natural Killer Cells Suppress T Cell-Associated Tumor Immune Evasion.

Natural Killer Cells Suppress T Cell-Associated Tumor Immune Evasion.

Publication date: Sep 10, 2019

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, A.J., Vervoort, S.J., Ramsbottom, K.M., Kelly, M.J., Michie, J., Pijpers, L., Johnstone, R.W., Kearney, C.J., and Oliaro, J. Natural Killer Cells Suppress T Cell-Associated Tumor Immune Evasion. 24062. 2019 Cell Rep (28):11.

Concepts Keywords
Antigen Presentation Killer tumor
Blockade Deficient melanoma
Cas9 Immunotherapy
CRISPR Immunotherapies
Genome Branches of biology
Immunotherapies Medical specialties
Interferon Medicine
Jak1 Immune system
Melanoma Antivirals
MHC Cytokines
MHC I Lymphocytes
Natural Killer Cancer treatments
Tumor Natural killer cell
MHC class I


Type Source Name
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
disease DOID cancer
disease MESH cancer
drug DRUGBANK Spinosad
disease MESH Tumor Immune Evasion


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