Downregulation of KEAP1 in melanoma promotes resistance to immune checkpoint blockade

Downregulation of KEAP1 in melanoma promotes resistance to immune checkpoint blockade

Abstract 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 KE...

Full description

Bibliographic Details
Main Authors: Douglas B. Fox, Richard Y. Ebright, Xin Hong, Hunter C. Russell, Hongshan Guo, Thomas J. LaSalle, Ben S. Wittner, Nicolas Poux, Joanna A. Vuille, Mehmet Toner, Nir Hacohen, Genevieve M. Boland, Debattama R. Sen, Ryan J. Sullivan, Shyamala Maheswaran, Daniel A. Haber
Format: Article
Language:English
Published: Nature Portfolio 2023-03-01
Series:npj Precision Oncology
Online Access:https://doi.org/10.1038/s41698-023-00362-3
Description
Summary:Abstract 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.
ISSN:2397-768X

Similar Items