Downregulation of KEAP1 in melanoma promotes resistance to immune checkpoint blockade.

Fox, Douglas B; Ebright, Richard Y; Hong, Xin; Russell, Hunter C; Guo, Hongshan; LaSalle, Thomas J; Wittner, Ben S; Poux, Nicolas; Vuille, Joanna A; Toner, Mehmet; Hacohen, Nir; Boland, Genevieve M; Sen, Debattama R; Sullivan, Ryan J; Maheswaran, Shyamala; Haber, Daniel A

Fox, Douglas B; Ebright, Richard Y; Hong, Xin; Russell, Hunter C; Guo, Hongshan; LaSalle, Thomas J; Wittner, Ben S; Poux, Nicolas; Vuille, Joanna A; Toner, Mehmet; Hacohen, Nir; Boland, Genevieve M; Sen, Debattama R; Sullivan, Ryan J; Maheswaran, Shyamala; Haber, Daniel A.

Afiliação

Fox DB; Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, 02114, USA.
Ebright RY; Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, 02114, USA.
Hong X; Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, 02114, USA.
Russell HC; Department of Biochemistry, School of Medicine and Key University Laboratory of Metabolism and Health of Guangdong, Southern University of Science and Technology, Shenzhen, 518055, China.
Guo H; Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, 02114, USA.
LaSalle TJ; Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, 02114, USA.
Wittner BS; Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, 311121, China.
Poux N; Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, 02114, USA.
Vuille JA; Broad Institute of Harvard and MIT, Cambridge, MA, 02139, USA.
Toner M; Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, 02114, USA.
Hacohen N; Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, 02114, USA.
Boland GM; Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, 02114, USA.
Sen DR; Center for Engineering in Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Sullivan RJ; Shriners Hospitals for Children, Boston, MA, 02114, USA.
Maheswaran S; Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA.
Haber DA; Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, 02114, USA.

NPJ Precis Oncol ; 7(1): 25, 2023 Mar 02.

Article em En | MEDLINE | ID: mdl-36864091

RESUMO

Immune checkpoint blockade (ICB) has demonstrated efficacy in patients with melanoma, but many exhibit poor responses. Using single cell RNA sequencing of melanoma patient-derived circulating tumor cells (CTCs) and functional characterization using mouse melanoma models, we show that the KEAP1/NRF2 pathway modulates sensitivity to ICB, independently of tumorigenesis. The NRF2 negative regulator, KEAP1, shows intrinsic variation in expression, leading to tumor heterogeneity and subclonal resistance.

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Texto completo: 1 Bases de dados: MEDLINE Idioma: En Revista: NPJ Precis Oncol Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos