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

Author:

Ruscetti Marcus1ORCID,Leibold Josef1ORCID,Bott Matthew J.1ORCID,Fennell Myles1,Kulick Amanda2,Salgado Nelson R.1,Chen Chi-Chao1ORCID,Ho Yu-jui1,Sanchez-Rivera Francisco J.1,Feucht Judith3,Baslan Timour1,Tian Sha1ORCID,Chen Hsuan-An1,Romesser Paul B.1ORCID,Poirier John T.24ORCID,Rudin Charles M.24ORCID,de Stanchina Elisa2ORCID,Manchado Eusebio1,Sherr Charles J.56ORCID,Lowe Scott W.16ORCID

Affiliation:

1. Department of Cancer Biology and Genetics, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

2. Department of Molecular Pharmacology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

3. Center for Cell Engineering and Immunology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

4. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.

5. Department of Tumor Cell Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA.

6. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.

Abstract

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

Funder

National Institutes of Health

Howard Hughes Medical Institute

National Cancer Institute

Memorial Sloan-Kettering Cancer Center

American Cancer Society

American Association for Thoracic Surgery

Stand Up To Cancer

Geoffrey Beene Cancer Research Center

German Research Foundation

William C. and Joyce C. O'Neil Charitable Trust

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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