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In vivo CRISPR screening in head and neck cancer reveals Uchl5 as an immunotherapy target

UCHL5 is a deubiquitinating enzyme that cleaves Lys-48-linked polyubiquitin chains. Here, the authors discover through in-vivo CRISPR-Cas9 screens that Uchl5 is involved in immune evasion and modulation of extracellular matrix deposition in head and neck squamous cell carcinoma.

Cong Fu
Robert Saddawi-Konefka
Robert T. Manguso
ResearchOpen Access29 Sept 2025
Nature Communications

Volume: 16, P: 1-18
In vivo CRISPR screens identify modifiers of CAR T cell function in myeloma

In vivo loss-of-function CRISPR screens were performed to identify genes influencing CAR T cell persistence and function in human multiple myeloma, highlighting CDKN1B as a promising target.

Nelson H. Knudsen
Giulia Escobar
Marcela V. Maus
Research24 Sept 2025
Nature

P: 1-10
The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunity

An orally bioavailable small-molecule active-site inhibitor of the phosphatases PTPN2 and PTPN1, ABBV-CLS-484, demonstrates immunotherapeutic efficacy in mouse models of cancer resistant to PD-1 blockade.

Christina K. Baumgartner
Hakimeh Ebrahimi-Nik
Robert T. Manguso
ResearchOpen Access04 Oct 2023
Nature

Volume: 622, P: 850-862
Targeting TBK1 to overcome resistance to cancer immunotherapy

Targeting TBK1 is an effective strategy to overcome resistance to cancer immunotherapy.

Yi Sun
Or-yam Revach
Russell W. Jenkins
Research12 Jan 2023
Nature

Volume: 615, P: 158-167
Epigenetic silencing by SETDB1 suppresses tumour intrinsic immunogenicity

A CRISPR–Cas9 screen of chromatin regulators in mouse tumour models treated with immune checkpoint blockade identifies SETDB1 as an epigenetic checkpoint protein that suppresses tumour-intrinsic immunogenicity.

Gabriel K. Griffin
Jingyi Wu
Bradley E. Bernstein
Research05 May 2021
Nature

Volume: 595, P: 309-314
Author Correction: Subsets of exhausted CD8⁺ T cells differentially mediate tumor control and respond to checkpoint blockade

Brian C. Miller
Debattama R. Sen
W. Nicholas Haining
Amendments and Corrections03 Oct 2019
Nature Immunology

Volume: 20, P: 1556
Loss of ADAR1 in tumours overcomes resistance to immune checkpoint blockade

Deletion of the A-to-I double-stranded RNA-editing enzyme ADAR1 sensitizes tumour cells to immunotherapy.

Jeffrey J. Ishizuka
Robert T. Manguso
W. Nicholas Haining
Research17 Dec 2018
Nature

Volume: 565, P: 43-48
In vivo CRISPR screens reveal the landscape of immune evasion pathways across cancer

Here, the authors use genome-scale in vivo CRISPR screens to look at immune evasion mechanisms across cancer models, showing that IFN-mediated upregulation of classical and non-classical MHC class I inhibitory checkpoints facilitate immune escape.

Juan Dubrot
Peter P. Du
Robert T. Manguso
Research23 Sept 2022
Nature Immunology

Volume: 23, P: 1495-1506
Leukemia-intrinsic determinants of CAR-T response revealed by iterative in vivo genome-wide CRISPR screening

CAR-T therapy is a promising treatment modality for B-cell malignancies, yet many patients relapse. Using an in vivo genomewide screen in a model of B cell leukemia, we identify an unexpected mechanism of CAR-T resistance in which interferon gamma from the in vivo tumor microenvironment induces an adaptive T-cell resistance program in tumor cells.

Azucena Ramos
Catherine E. Koch
Michael T. Hemann
ResearchOpen Access05 Dec 2023
Nature Communications

Volume: 14, P: 1-21
Subsets of exhausted CD8⁺ T cells differentially mediate tumor control and respond to checkpoint blockade

Exhausted cytotoxic T lymphocytes (CTLs) express the receptor PD-1 as a key signature. Haining and colleagues show that there are different ‘depths’ of exhaustion with a subset of exhausted CTLs that retain polyfunctionality and are responsive to PD-1 blockade.

Brian C. Miller
Debattama R. Sen
W. Nicholas Haining
Research18 Feb 2019
Nature Immunology

Volume: 20, P: 326-336
ERK1/2 phosphorylation predicts survival following anti-PD-1 immunotherapy in recurrent glioblastoma

In two cohorts of patients with glioblastoma who received anti-PD-1, Sonabend and colleagues show that ERK1/2 phosphorylation, detected by immunohistochemistry, provides a biomarker for MAPK/ERK pathway activity and better survival on this therapy.

Víctor A. Arrieta
Andrew X. Chen
Adam M. Sonabend
Research29 Nov 2021
Nature Cancer

Volume: 2, P: 1372-1386
In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target

In vivo CRISPR screening reveals that loss of Ptpn2 increases the response of tumour cells to immunotherapy and increases IFNγ signalling, suggesting that PTPN2 inhibition may potentiate the effect of immunotherapies that invoke an IFNγ response.

Robert T. Manguso
Hans W. Pope
W. Nicholas Haining
Research19 Jul 2017
Nature

Volume: 547, P: 413-418

Search

In vivo CRISPR screening in head and neck cancer reveals Uchl5 as an immunotherapy target

In vivo CRISPR screens identify modifiers of CAR T cell function in myeloma

The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunity

Targeting TBK1 to overcome resistance to cancer immunotherapy

Epigenetic silencing by SETDB1 suppresses tumour intrinsic immunogenicity

Author Correction: Subsets of exhausted CD8⁺ T cells differentially mediate tumor control and respond to checkpoint blockade

Loss of ADAR1 in tumours overcomes resistance to immune checkpoint blockade

In vivo CRISPR screens reveal the landscape of immune evasion pathways across cancer

Leukemia-intrinsic determinants of CAR-T response revealed by iterative in vivo genome-wide CRISPR screening

Subsets of exhausted CD8⁺ T cells differentially mediate tumor control and respond to checkpoint blockade

ERK1/2 phosphorylation predicts survival following anti-PD-1 immunotherapy in recurrent glioblastoma

In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target

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