Abstract PO039: Cancer cells educate natural killer cells to a metastasis-promoting cell state

摘要: Natural killer (NK) cells have potent antitumor and antimetastatic activity. It is incompletely understood how cancer escape NK cell surveillance. Using ex vivo in models of metastasis, we establish that keratin-14+ breast are vulnerable to cells. We then discovered exposure causes lose their cytotoxic ability promote metastatic outgrowth. Gene expression comparisons revealed healthy an active molecular phenotype, whereas tumor-exposed (teNK) resemble resting Receptor–ligand analysis between teNK tumor multiple potential targets. next showed treatment with antibodies targeting TIGIT, KLRG1, or small-molecule inhibitors DNA methyltransferases (DMNT) each reduced colony formation. Combinations DNMT anti-TIGIT anti-KLRG1 further potential. propose NK-directed therapies these pathways would be effective the adjuvant setting prevent recurrence. Citation Format: Isaac S. Chan, Hildur Knutsdottir, Gayathri Ramakrishnan, Veena Padmanaban, Manisha Warrier, Juan Carlos Ramirez, Matthew Dunworth, Hao Zhang, Elizabeth M. Jaffee, Joel Bader, Andrew J. Ewald. Cancer educate natural a metastasis-promoting state [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Immunol Res 2021;9(2 Suppl):Abstract nr PO039.