NK cell–mediated cytotoxicity contributes to tumor control by a cytostatic drug combination

• DOI: 10.1126/science.aas9090
• Publication Date: 2018-12-21T02:25:46Z
• Authors: Marcus Ruscetti; Josef Leibold; Matthew J. Bott; Myles Fennell; Amanda Kulick; Nelson R. Salgado; Chi-Chao Chen; Yu-jui Ho; Francisco J. Sanc...; Judith Feucht; Timour Baslan; Sha Tian; Hsuan-An Chen; Paul B. Romesser; John T. Poirier; Charles M. Rudin; Elisa de Stanchina; Eusebio Manchado; Charles J. Sherr; Scott W. Lowe
• Keywords: Cytotoxicity, Immunologic; 0301 basic medicine; Lung Neoplasms; Aminopyridines; Cyclin-Dependent Kinase 4; Apoptosis; Cyclin-Dependent Kinase 6; Cytostatic Agents; Intercellular Adhesion Molecule-1; 3. Good health; Killer Cells, Natural; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Antineoplastic Combined Chemotherapy Protocols; Mutation; Animals; Humans; Benzimidazoles; Molecular Targeted Therapy; Mitogen-Activated Protein Kinases; Immunologic Surveillance; Cellular Senescence

Small molecules spark NK cell response Immunotherapy is a powerful treatment for certain cancers. Yet those patients that do not respond, simultaneous strategies mobilize the immune system and directly target malignant cells may be more effective. Ruscetti et al. report combining two clinically approved cancer drugs promoted surveillance killing of KRAS-mutant lung tumors in mice (see Perspective by Cornen Vivier). The small molecules—a mitogen-activated protein kinase inhibitor cyclin-dependent 4/6 inhibitor—induced natural killer (NK) recruitment elimination senescent cells, which did occur when either agent was used alone. Science , this issue p. 1416 ; see also 1355