Natural Killer Cells Control Tumor Growth by Sensing a Growth Factor | Zendy

Alexander D. Barrow | Zendy; Melissa A. Edeling | Zendy; Vladimir Trifonov | Zendy; Jingqin Luo | Zendy; Piyush Goyal | Zendy; Benjamin P. Bohl | Zendy; Jennifer K. Bando | Zendy; Albert H. Kim | Zendy; John R. Walker | Zendy; Mary Andahazy | Zendy; Mattia Bugatti | Zendy; Laura Melocchi | Zendy; William Vermi | Zendy; Daved H. Fremont | Zendy; Sarah Cox | Zendy; Marina Cella | Zendy; Christian Schmedt | Zendy; Marco Colonna | Zendy

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Natural Killer Cells Control Tumor Growth by Sensing a Growth Factor

Author(s) -

Alexander D. Barrow,

Melissa A. Edeling,

Vladimir Trifonov,

Jingqin Luo,

Piyush Goyal,

Benjamin P. Bohl,

Jennifer K. Bando,

Albert H. Kim,

John R. Walker,

Mary Andahazy,

Mattia Bugatti,

Laura Melocchi,

William Vermi,

Daved H. Fremont,

Sarah Cox,

Marina Cella,

Christian Schmedt,

Marco Colonna

Publication year - 2017

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2017.11.037

Subject(s) - biology , autocrine signalling , paracrine signalling , stromal cell , cancer research , platelet derived growth factor receptor , growth factor , tumor necrosis factor alpha , platelet derived growth factor , innate immune system , natural killer cell , microbiology and biotechnology , immunology , immune system , cell culture , receptor , cytotoxic t cell , biochemistry , genetics , in vitro

Many tumors produce platelet-derived growth factor (PDGF)-DD, which promotes cellular proliferation, epithelial-mesenchymal transition, stromal reaction, and angiogenesis through autocrine and paracrine PDGFRβ signaling. By screening a secretome library, we found that the human immunoreceptor NKp44, encoded by NCR2 and expressed on natural killer (NK) cells and innate lymphoid cells, recognizes PDGF-DD. PDGF-DD engagement of NKp44 triggered NK cell secretion of interferon gamma (IFN)-γ and tumor necrosis factor alpha (TNF-α) that induced tumor cell growth arrest. A distinctive transcriptional signature of PDGF-DD-induced cytokines and the downregulation of tumor cell-cycle genes correlated with NCR2 expression and greater survival in glioblastoma. NKp44 expression in mouse NK cells controlled the dissemination of tumors expressing PDGF-DD more effectively than control mice, an effect enhanced by blockade of the inhibitory receptor CD96 or CpG-oligonucleotide treatment. Thus, while cancer cell production of PDGF-DD supports tumor growth and stromal reaction, it concomitantly activates innate immune responses to tumor expansion.

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