Therapeutically Increasing MHC-I Expression Potentiates Immune Checkpoint Blockade.


Journal

Cancer discovery
ISSN: 2159-8290
Titre abrégé: Cancer Discov
Pays: United States
ID NLM: 101561693

Informations de publication

Date de publication:
06 2021
Historique:
received: 07 06 2020
revised: 13 11 2020
accepted: 13 01 2021
pubmed: 17 2 2021
medline: 19 2 2022
entrez: 16 2 2021
Statut: ppublish

Résumé

Immune checkpoint blockade (ICB) therapy revolutionized cancer treatment, but many patients with impaired MHC-I expression remain refractory. Here, we combined FACS-based genome-wide CRISPR screens with a data-mining approach to identify drugs that can upregulate MHC-I without inducing PD-L1. CRISPR screening identified TRAF3, a suppressor of the NFκB pathway, as a negative regulator of MHC-I but not PD-L1. The

Identifiants

pubmed: 33589424
pii: 2159-8290.CD-20-0812
doi: 10.1158/2159-8290.CD-20-0812
pmc: PMC8543117
mid: NIHMS1666185
doi:

Substances chimiques

B7-H1 Antigen 0
Histocompatibility Antigens Class I 0
Immune Checkpoint Inhibitors 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1524-1541

Subventions

Organisme : NCI NIH HHS
ID : R01 CA234018
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA206963
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA101942
Pays : United States
Organisme : NHGRI NIH HHS
ID : T32 HG002295
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI137337
Pays : United States

Informations de copyright

©2021 American Association for Cancer Research.

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Auteurs

Shengqing Stan Gu (SS)

Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Wubing Zhang (W)

Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
School of Life Science and Technology, Tongji University, Shanghai, China.

Xiaoqing Wang (X)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Peng Jiang (P)

Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.

Nicole Traugh (N)

Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts.

Ziyi Li (Z)

Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
School of Life Science and Technology, Tongji University, Shanghai, China.

Clifford Meyer (C)

Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Blair Stewig (B)

Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts.

Yingtian Xie (Y)

Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts.

Xia Bu (X)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Michael P Manos (MP)

Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Alba Font-Tello (A)

Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts.

Evisa Gjini (E)

Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Ana Lako (A)

Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Klothilda Lim (K)

Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts.

Jake Conway (J)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Alok K Tewari (AK)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Zexian Zeng (Z)

Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Avinash Das Sahu (AD)

Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Collin Tokheim (C)

Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Jason L Weirather (JL)

Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Jingxin Fu (J)

Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
School of Life Science and Technology, Tongji University, Shanghai, China.

Yi Zhang (Y)

Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts.
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Benjamin Kroger (B)

The University of Texas Southwestern Medical School, Dallas, Texas.

Jin Hua Liang (JH)

Department of Microbiology, Harvard Medical School, Boston, Massachusetts.
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.

Paloma Cejas (P)

Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts.

Gordon J Freeman (GJ)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Scott Rodig (S)

Department of Pathologic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Henry W Long (HW)

Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts.

Benjamin E Gewurz (BE)

Department of Microbiology, Harvard Medical School, Boston, Massachusetts.
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.

F Stephen Hodi (FS)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Myles Brown (M)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. xsliu@ds.dfci.harvard.edu myles_brown@dfci.harvard.edu.
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts.

X Shirley Liu (XS)

Department of Data Science, Dana-Farber Cancer Institute, Boston, Massachusetts. xsliu@ds.dfci.harvard.edu myles_brown@dfci.harvard.edu.
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts.

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