Nature Communications (Mar 2023)
Checkpoint kinase 1/2 inhibition potentiates anti-tumoral immune response and sensitizes gliomas to immune checkpoint blockade
- Crismita Dmello,
- Junfei Zhao,
- Li Chen,
- Andrew Gould,
- Brandyn Castro,
- Victor A. Arrieta,
- Daniel Y. Zhang,
- Kwang-Soo Kim,
- Deepak Kanojia,
- Peng Zhang,
- Jason Miska,
- Ragini Yeeravalli,
- Karl Habashy,
- Ruth Saganty,
- Seong Jae Kang,
- Jawad Fares,
- Connor Liu,
- Gavin Dunn,
- Elizabeth Bartom,
- Matthew J. Schipma,
- Patrick D. Hsu,
- Mahmoud S. Alghamri,
- Maciej S. Lesniak,
- Amy B. Heimberger,
- Raul Rabadan,
- Catalina Lee-Chang,
- Adam M. Sonabend
Affiliations
- Crismita Dmello
- Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University
- Junfei Zhao
- Program for Mathematical Genomics, Department of Systems Biology, Columbia University
- Li Chen
- Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University
- Andrew Gould
- Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University
- Brandyn Castro
- Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University
- Victor A. Arrieta
- Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University
- Daniel Y. Zhang
- Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University
- Kwang-Soo Kim
- Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University
- Deepak Kanojia
- Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University
- Peng Zhang
- Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University
- Jason Miska
- Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University
- Ragini Yeeravalli
- Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University
- Karl Habashy
- Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University
- Ruth Saganty
- Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University
- Seong Jae Kang
- Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University
- Jawad Fares
- Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University
- Connor Liu
- Department of Neurological Surgery, Washington University School of Medicine
- Gavin Dunn
- Department of Neurological Surgery, Washington University School of Medicine
- Elizabeth Bartom
- Department of Biochemistry and Molecular Genetics, Northwestern University
- Matthew J. Schipma
- NUSeq Core, Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University
- Patrick D. Hsu
- Innovative Genomics Institute, University of California, Berkeley
- Mahmoud S. Alghamri
- Department of Neurosurgery, University of Michigan Medical School
- Maciej S. Lesniak
- Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University
- Amy B. Heimberger
- Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University
- Raul Rabadan
- Program for Mathematical Genomics, Department of Systems Biology, Columbia University
- Catalina Lee-Chang
- Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University
- Adam M. Sonabend
- Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University
- DOI
- https://doi.org/10.1038/s41467-023-36878-2
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 18
Abstract
Immunotherapies have shown limited efficacy in patients with glioma. Here, based on an in vivo kinome knockout CRISPR screen, the authors show that checkpoint kinase 2 promotes CD8 T cell immune evasion and that its depletion or inhibition improve survival and response to PD1/PDL1 blockade in preclinical glioma models.
