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Article: Immunogenic Death of Hepatocellular Carcinoma Cells in Mice Expressing Caspase-Resistant ROCK1 Is Not Replicated by ROCK Inhibitors.

Naylor, Gregory / Julian, Linda / Watson-Bryce, Steven / Mullin, Margaret / Nibbs, Robert J / Olson, Michael F

2022 Volume 14, Issue 23

Abstract: The morphological changes during apoptosis help facilitate "immunologically silent" cell death. Caspase cleavage of the ROCK1 kinase results in its activation, which drives the forceful contraction of apoptotic cells. We previously showed that when ROCK1 ...

Abstract	The morphological changes during apoptosis help facilitate "immunologically silent" cell death. Caspase cleavage of the ROCK1 kinase results in its activation, which drives the forceful contraction of apoptotic cells. We previously showed that when ROCK1 was mutated to render it caspase-resistant, there was greater liver damage and neutrophil recruitment after treatment with the hepatotoxin diethylnitrosamine (DEN). We now show that acute DEN-induced liver damage induced higher levels of pro-inflammatory cytokines/chemokines, indicative of immunogenic cell death (ICD), in mice expressing non-cleavable ROCK1 (ROCK1nc). Hepatocellular carcinoma (HCC) tumours in ROCK1nc mice had more neutrophils and CD8
Language	English
Publishing date	2022-11-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14235943
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Article ; Online: Co-inhibition of TGF-β and PD-L1 pathways in a metastatic colorectal cancer mouse model triggers interferon responses, innate cells and T cells, alongside metabolic changes and tumor resistance.

Nair, Reshmi / Lannagan, Tamsin R M / Jackstadt, Rene / Andrusaite, Anna / Cole, John / Boyne, Caitlin / Nibbs, Robert J B / Sansom, Owen J / Milling, Simon

Oncoimmunology

2024 Volume 13, Issue 1, Page(s) 2330194

Abstract: Colorectal cancer (CRC) is the third most prevalent cancer worldwide with a high mortality rate (20-30%), especially due to metastasis to adjacent organs. Clinical responses to chemotherapy, radiation, targeted and immunotherapies are limited to a subset ...

Abstract	Colorectal cancer (CRC) is the third most prevalent cancer worldwide with a high mortality rate (20-30%), especially due to metastasis to adjacent organs. Clinical responses to chemotherapy, radiation, targeted and immunotherapies are limited to a subset of patients making metastatic CRC (mCRC) difficult to treat. To understand the therapeutic modulation of immune response in mCRC, we have used a genetically engineered mouse model (GEMM), "KPN", which resembles the human 'CMS4'-like subtype. We show here that transforming growth factor (TGF-β1), secreted by KPN organoids, increases cancer cell proliferation, and inhibits splenocyte activation
MeSH term(s)	Mice ; Animals ; Humans ; Transforming Growth Factor beta1 ; Transforming Growth Factor beta/metabolism ; Interferons ; B7-H1 Antigen/genetics ; T-Lymphocytes, Cytotoxic/metabolism ; Colonic Neoplasms ; Rectal Neoplasms
Chemical Substances	Transforming Growth Factor beta1 ; Transforming Growth Factor beta ; Interferons (9008-11-1) ; B7-H1 Antigen
Language	English
Publishing date	2024-03-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2645309-5
ISSN	2162-402X ; 2162-402X
ISSN (online)	2162-402X
ISSN	2162-402X
DOI	10.1080/2162402X.2024.2330194
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Article ; Online: Understanding and overcoming the resistance of cancer to PD-1/PD-L1 blockade.

Shergold, Amy L / Millar, Rhona / Nibbs, Robert J B

Pharmacological research

2019 Volume 145, Page(s) 104258

Abstract: Greater understanding of tumour immunobiology has led to a new era of cancer treatment in which immuno-oncology (IO) therapies are used to boost anti-cancer immune responses. Prominent among these therapies are immune checkpoint inhibitors (ICIs), ... ...

Abstract	Greater understanding of tumour immunobiology has led to a new era of cancer treatment in which immuno-oncology (IO) therapies are used to boost anti-cancer immune responses. Prominent among these therapies are immune checkpoint inhibitors (ICIs), antibody-based drugs that can unleash the power of tumour-specific CD8 + T-cells. ICIs targeting the Programmed cell death protein 1 (PD-1) cell surface receptor or its ligand PD-L1 are particularly effective, with clinical studies reporting powerful and durable therapeutic impact against many cancer types, including melanoma and non-small cell lung cancer. ICIs have the potential to transform the landscape of cancer treatment, and their development was recognised by the award of the 2018 Nobel Prize in Physiology or Medicine to James Allison and Tasuku Honjo. However, the proportion of patients responding to anti-PD-1/PD-L1 monotherapy can be low. The next major challenge involves understanding and overcoming the innate and acquired resistance that prevents most patients from responding to PD-1/PD-L1 blockade. In this review, we outline the physiological function of PD-1 and its exploitation by developing tumours. We give an overview of current FDA-approved drugs targeting PD-1 or PD-L1 and summarise clinical progress so far. We then discuss key mechanisms thought to underpin resistance to PD-1/PD-L1 blockade, describing biomarkers that could allow patient responses to be predicted before treatment, and tracked once treatment has started. We also present clinical and pre-clinical combination therapies that have been developed to overcome resistance and which have the potential to substantially extend the therapeutic reach of these revolutionary drugs.
MeSH term(s)	Animals ; Antineoplastic Agents, Immunological/therapeutic use ; B7-H1 Antigen/antagonists & inhibitors ; B7-H1 Antigen/immunology ; Drug Resistance, Neoplasm/drug effects ; Humans ; Immune Evasion/drug effects ; Neoplasms/drug therapy ; Neoplasms/immunology ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Programmed Cell Death 1 Receptor/immunology ; T-Lymphocytes/immunology
Chemical Substances	Antineoplastic Agents, Immunological ; B7-H1 Antigen ; Programmed Cell Death 1 Receptor
Language	English
Publishing date	2019-05-04
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1003347-6
ISSN	1096-1186 ; 0031-6989 ; 1043-6618
ISSN (online)	1096-1186
ISSN	0031-6989 ; 1043-6618
DOI	10.1016/j.phrs.2019.104258
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Article: A guide to chemokines and their receptors

Hughes, Catherine E / Nibbs, Robert J. B

FEBS journal. 2018 Aug., v. 285, no. 16

2018

Abstract: The chemokines (or chemotactic cytokines) are a large family of small, secreted proteins that signal through cell surface G protein‐coupled heptahelical chemokine receptors. They are best known for their ability to stimulate the migration of cells, most ... ...

Abstract	The chemokines (or chemotactic cytokines) are a large family of small, secreted proteins that signal through cell surface G protein‐coupled heptahelical chemokine receptors. They are best known for their ability to stimulate the migration of cells, most notably white blood cells (leukocytes). Consequently, chemokines play a central role in the development and homeostasis of the immune system, and are involved in all protective or destructive immune and inflammatory responses. Classically viewed as inducers of directed chemotactic migration, it is now clear that chemokines can stimulate a variety of other types of directed and undirected migratory behavior, such as haptotaxis, chemokinesis, and haptokinesis, in addition to inducing cell arrest or adhesion. However, chemokine receptors on leukocytes can do more than just direct migration, and these molecules can also be expressed on, and regulate the biology of, many nonleukocytic cell types. Chemokines are profoundly affected by post‐translational modification, by interaction with the extracellular matrix (ECM), and by binding to heptahelical ‘atypical’ chemokine receptors that regulate chemokine localization and abundance. This guide gives a broad overview of the chemokine and chemokine receptor families; summarizes the complex physical interactions that occur in the chemokine network; and, using specific examples, discusses general principles of chemokine function, focusing particularly on their ability to direct leukocyte migration.
Keywords	cell movement ; chemokine receptors ; chemokines ; chemotaxis ; extracellular matrix ; homeostasis ; inflammation ; leukocytes ; post-translational modification
Language	English
Dates of publication	2018-08
Size	p. 2944-2971.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	REVIEW
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.14466
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Article ; Online: A guide to chemokines and their receptors.

Hughes, Catherine E / Nibbs, Robert J B

The FEBS journal

2018 Volume 285, Issue 16, Page(s) 2944–2971

Abstract: The chemokines (or chemotactic cytokines) are a large family of small, secreted proteins that signal through cell surface G protein-coupled heptahelical chemokine receptors. They are best known for their ability to stimulate the migration of cells, most ... ...

Abstract	The chemokines (or chemotactic cytokines) are a large family of small, secreted proteins that signal through cell surface G protein-coupled heptahelical chemokine receptors. They are best known for their ability to stimulate the migration of cells, most notably white blood cells (leukocytes). Consequently, chemokines play a central role in the development and homeostasis of the immune system, and are involved in all protective or destructive immune and inflammatory responses. Classically viewed as inducers of directed chemotactic migration, it is now clear that chemokines can stimulate a variety of other types of directed and undirected migratory behavior, such as haptotaxis, chemokinesis, and haptokinesis, in addition to inducing cell arrest or adhesion. However, chemokine receptors on leukocytes can do more than just direct migration, and these molecules can also be expressed on, and regulate the biology of, many nonleukocytic cell types. Chemokines are profoundly affected by post-translational modification, by interaction with the extracellular matrix (ECM), and by binding to heptahelical 'atypical' chemokine receptors that regulate chemokine localization and abundance. This guide gives a broad overview of the chemokine and chemokine receptor families; summarizes the complex physical interactions that occur in the chemokine network; and, using specific examples, discusses general principles of chemokine function, focusing particularly on their ability to direct leukocyte migration.
MeSH term(s)	Animals ; Cell Movement ; Chemokines/genetics ; Chemokines/metabolism ; Chemotaxis ; Glycosaminoglycans/metabolism ; Homeostasis ; Host-Pathogen Interactions/physiology ; Humans ; Infections/etiology ; Inflammation/etiology ; Protein Multimerization ; Protein Processing, Post-Translational ; Receptors, Chemokine/genetics ; Receptors, Chemokine/metabolism
Chemical Substances	Chemokines ; Glycosaminoglycans ; Receptors, Chemokine
Language	English
Publishing date	2018-04-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.14466
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Article: Chemokine Transport Dynamics and Emerging Recognition of Their Role in Immune Function.

Moore, James E / Brook, Bindi S / Nibbs, Robert J B

Current opinion in biomedical engineering

2018 Volume 5, Page(s) 90–95

Abstract: Leukocyte migration is critically important during all protective and pathological immune and inflammatory responses. Chemokines play fundamental roles in this process, and chemokine concentration gradients stimulate the directional migration of ... ...

Abstract	Leukocyte migration is critically important during all protective and pathological immune and inflammatory responses. Chemokines play fundamental roles in this process, and chemokine concentration gradients stimulate the directional migration of leukocytes. The formation and regulation of these gradients is poorly understood. These are complex processes that depend on the specific properties of each chemokine and interactions between physical, biological and biochemical processes, including production, diffusion, advection, scavenging, post-translational modification, and extracellular matrix (ECM) binding. While some of these mechanisms have been investigated in isolation or limited combinations, more integrative research is required to provide a quantitative knowledge base that explains how chemokine gradients are established and maintained, and how cells respond to, and modify, these gradients.
Language	English
Publishing date	2018-03-20
Publishing country	England
Document type	Journal Article
ISSN	2468-4511
ISSN	2468-4511
DOI	10.1016/j.cobme.2018.03.001
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Article ; Online: Immunological roles of intestinal mesenchymal cells.

Thomson, Carolyn A / Nibbs, Robert J / McCoy, Kathy D / Mowat, Allan Mcl

Immunology

2020 Volume 160, Issue 4, Page(s) 313–324

Abstract: The intestine is continuously exposed to an enormous variety and quantity of antigens and innate immune stimuli derived from both pathogens and harmless materials, such as food and commensal bacteria. Accordingly, the intestinal immune system is uniquely ...

Abstract	The intestine is continuously exposed to an enormous variety and quantity of antigens and innate immune stimuli derived from both pathogens and harmless materials, such as food and commensal bacteria. Accordingly, the intestinal immune system is uniquely adapted to ensure appropriate responses to the different kinds of challenge; maintaining tolerance to harmless antigens in the steady-state, whilst remaining poised to deal with potential pathogens. To accomplish this, leucocytes of the intestinal immune system have to adapt to a constantly changing environment and interact with many different non-leucocytic intestinal cell types, including epithelial and endothelial cells, neurons, and a heterogenous network of intestinal mesenchymal cells (iMC). These interactions are intricately involved in the generation of protective immunity, the elaboration of inflammatory responses, and the development of inflammatory conditions, such as inflammatory bowel diseases. Here we discuss recent insights into the immunological functions of iMC under homeostatic and inflammatory conditions, focusing particularly on iMC in the mucosa and submucosa, and highlighting how an appreciation of the immunology of iMC may help understand the pathogenesis and treatment of disease.
MeSH term(s)	Animals ; Homeostasis ; Humans ; Immune Tolerance ; Immunity ; Inflammation/immunology ; Inflammatory Bowel Diseases/immunology ; Intestinal Mucosa/immunology ; Intestines/immunology ; Mesenchymal Stem Cells/immunology
Language	English
Publishing date	2020-04-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80124-0
ISSN	1365-2567 ; 0019-2805 ; 0953-4954
ISSN (online)	1365-2567
ISSN	0019-2805 ; 0953-4954
DOI	10.1111/imm.13191
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Article: Regulation of the Adaptive Immune Response by the IκB Family Protein Bcl-3.

Herrington, Felicity D / Nibbs, Robert J B

Cells

2016 Volume 5, Issue 2

Abstract: Bcl-3 is a member of the IκB family of proteins and an important regulator of Nuclear Factor (NF)-κB activity. The ability of Bcl-3 to bind and regulate specific NF-κB dimers has been studied in great depth, but its physiological roles in vivo are still ... ...

Abstract	Bcl-3 is a member of the IκB family of proteins and an important regulator of Nuclear Factor (NF)-κB activity. The ability of Bcl-3 to bind and regulate specific NF-κB dimers has been studied in great depth, but its physiological roles in vivo are still not fully understood. It is, however, becoming clear that Bcl-3 is essential for the proper development, survival and activity of adaptive immune cells. Bcl-3 dysregulation can be observed in a number of autoimmune pathologies, and Bcl3-deficient animals are more susceptible to bacterial and parasitic infection. This review will describe our current understanding of the roles played by Bcl-3 in the development and regulation of the adaptive immune response, including lymphoid organogenesis, immune tolerance, lymphocyte function and dendritic cell biology.
Language	English
Publishing date	2016-03-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2661518-6
ISSN	2073-4409
ISSN	2073-4409
DOI	10.3390/cells5020014
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Article ; Online: A Comprehensive Profile of Chemokine Gene Expression in the Tissues of the Female Reproductive Tract in Mice.

Menzies, Fiona M / Oldham, Rachel S / Waddell, Carolann / Nelson, Scott M / Nibbs, Robert J B

Immunological investigations

2019 Volume 49, Issue 3, Page(s) 264–286

Abstract: Homeostatic leukocyte trafficking into and within the female reproductive tract (FRT) contributes to fertility and reproductive health. It is unclear how this process is regulated in the anatomically distinct reproductive tissues, or whether the genes ... ...

Abstract	Homeostatic leukocyte trafficking into and within the female reproductive tract (FRT) contributes to fertility and reproductive health. It is unclear how this process is regulated in the anatomically distinct reproductive tissues, or whether the genes involved are affected by cyclical changes in reproductive hormones. In tissues such as skin and intestine, mouse studies have defined evolutionarily conserved molecular mechanisms for tissue-specific homing, interstitial positioning, and leukocyte egress. Chemokine family members are invariably involved, with the chemokine expression profile of a tissue regulating leukocyte content. Reproductive tissues (ovary, vagina, cervix, uterine horn) of 8 week old virgin female C57BL/6 mice (
MeSH term(s)	Animals ; Chemokines/genetics ; Estrous Cycle/immunology ; Female ; Gene Expression Profiling ; Genitalia, Female/cytology ; Genitalia, Female/metabolism ; Leukocytes/metabolism ; Mice ; Mice, Inbred C57BL ; Myeloid Cells/metabolism ; Organ Specificity/immunology
Chemical Substances	Chemokines
Language	English
Publishing date	2019-08-20
Publishing country	England
Document type	Journal Article
ZDB-ID	632565-8
ISSN	1532-4311 ; 0882-0139
ISSN (online)	1532-4311
ISSN	0882-0139
DOI	10.1080/08820139.2019.1655573
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Article ; Online: HIV: getting to the heart of DARCness.

Nibbs, Robert J B

Blood

2009 Volume 114, Issue 13, Page(s) 2570–2571

Language	English
Publishing date	2009-09-24
Publishing country	United States
Document type	Comment ; Journal Article
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2009-08-235556
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