Table Of ContentAdvances in Experimental Medicine and Biology 1060
Benjamin M.J Owens
Matthew A. Lakins Editors
Stromal
Immunology
Advances in Experimental Medicine and Biology
Editorial Board:
IRUN R. COHEN, The Weizmann Institute of Science, Rehovot, Israel
ABEL LAJTHA, N.S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA
JOHN D. LAMBRIS, University of Pennsylvania, Philadelphia, PA, USA
RODOLFO PAOLETTI, University of Milan, Milan, Italy
NIMA REZAEI, Tehran University of Medical Sciences, Tehran, Iran
More information about this series at http://www.springer.com/series/5584
Benjamin M.J Owens • Matthew A. Lakins
Editors
Stromal Immunology
Editors
Benjamin M.J Owens Matthew A. Lakins
Somerville College F-star Biotechnology Ltd.,
University of Oxford Babraham Research Campus
Oxford, UK Cambridge, UK
EUSA Pharma
Hemel Hempstead
Hertfordshire, UK
ISSN 0065-2598 ISSN 2214-8019 (electronic)
Advances in Experimental Medicine and Biology
ISBN 978-3-319-78125-9 ISBN 978-3-319-78127-3 (eBook)
https://doi.org/10.1007/978-3-319-78127-3
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Preface
The concept for this book arose as a result of growing interest in the investigation of
non-hematopoietic stromal cells and their impact on immune responses. Through
interactions during diverse doctoral and postdoctoral research programmes spanning
several years at the University of York, the University of Cambridge and the
University of Oxford, we recognised a need for a cohesive group to bring together
scientists interested in the concepts underlying stromal immunology, and the
Stromal Immunology Group (StIG) was born.
Having organised several successful international StIG conferences, we felt that
a missing part of the picture was an advanced book comprising a collection of writ-
ings from leaders in stromal immunology that could act as a primer for professional
researchers new to this specialist field. This book would also provide support for the
teaching of graduate and undergraduate students in science and medicine.
What follows is the collected work of scientists and physicians from across the
world, all of whom share a belief in the huge potential for research into stromal
immunology to contribute to medical research. Topics covered range from the inter-
action between leukocytes and lymph node stromal cells, inflammatory responses of
mesenchymal stem cells and fibroblasts to the key roles of stromal cells in response
to infection, the tumour microenvironment and the healthy and inflamed intestine.
Important avenues for future research are addressed, as are the uses of advanced cell
culture systems for the investigation of human tissue stromal cell function and stro-
mal cell targeting for therapeutic benefit.
Numerous studies have addressed the significant therapeutic potential of exploit-
ing stromal cells in combating disease. Pancreatic cancer, for example, and specifi-
cally pancreatic ductal adenocarcinoma (PDAC), is a stromal-rich, lethal malignancy
fundamentally resistant to standard of care therapies. Much work has been carried
out targeting the desmoplasmic nature of PDAC, particularly the cancer-associated
fibroblast and endothelial cell containing component. Whilst strategies aimed at
depleting these cell types to aid drug perfusion and immune cell infiltration work
well in murine models, the translatability of such approaches remains in question.
This approach is not limited to pancreatic cancer. Many other stromal-rich
tumours which employ a highly desmoplastic stroma as a physical barrier to immune
v
vi Preface
cell infiltration could be treated in such a way. Breast, prostate, and colon cancer all
recruit and influence their tumour microenvironment in order to regulate immune
escape, promote metastasis and aid progression. These cancers, and more recently
others such as non-small cell lung carcinoma, are put through a prognostic test
evaluating their tumour:stroma ratio and the outcome is used to successfully predict
prognosis and the chances of relapse. Soon, tools such as the tumour:stroma ratio
measurement could serve as an influencing factor on suggested treatment and
whether targeting the stroma is a valid approach for those specific diseases.
Similarly, gaining a deeper understanding of specific mediators of stromal cell
activation in chronically inflamed tissue – such as the recent discovery of Oncostatin
M as a driver of intestinal stromal cell activation during inflammatory bowel dis-
ease – may lead to the identification of novel therapeutic axes that can be targeted
to revolutionise therapy for patients with these debilitating inflammatory
conditions.
We hope that this introduction to advanced concepts in stromal immunology
serves as a useful, stimulating and enjoyable tool for those with an interest in
learning more about this exciting area of immunology, and we look forward to
seeing the field expand and grow over the coming years.
And remember, ‘It’s all about the Stroma’
Oxford, UK Benjamin M.J Owens
Hertfordshire, UK
Cambridge, UK Matthew A. Lakins
Acknowledgements
This textbook was produced as a collaboration between the British Society for
Immunology, the BSI Stromal Immunology Group and Springer Publishing,
USA. We are indebted to all the authors for their valuable contributions.
vii
Contents
1 Leukocyte-Stromal Interactions Within Lymph Nodes . . . . . . . . . . . . 1
Joshua D’Rozario, David Roberts, Muath Suliman,
Konstantin Knoblich, and Anne Fletcher
2 Stromal Cell Responses in Infection . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
Paul M. Kaye
3 Fibroblasts and Osteoblasts in Inflammation and Bone Damage . . . 37
Jason D. Turner, Amy J. Naylor, Christopher Buckley,
Andrew Filer, and Paul-Peter Tak
4 Molecular and Cellular Requirements for the Assembly
of Tertiary Lymphoid Structures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55
C. G. Mueller, S. Nayar, J. Campos, and F. Barone
5 Mesenchymal Stem Cells as Endogenous Regulators
of Inflammation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
Hafsa Munir, Lewis S. C. Ward, and Helen M. McGettrick
6 Stromal Cells in the Tumor Microenvironment . . . . . . . . . . . . . . . . . . 99
Alice E. Denton, Edward W. Roberts, and Douglas T. Fearon
7 Immunosuppression by Intestinal Stromal Cells . . . . . . . . . . . . . . . . . 115
Iryna V. Pinchuk and Don W. Powell
8 Novel Models to Study Stromal Cell- Leukocyte
Interactions in Health and Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131
Mattias Svensson and Puran Chen
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
ix
Contributors
F. Barone Rheumatology Research Group, Institute of Inflammation and Ageing
(IIA), University of Birmingham, Birmingham, UK
Christopher Buckley Rheumatology Research Group, Institute for Inflammation
and Ageing, College of Medical and Dental Sciences, University of Birmingham,
Queen Elizabeth Hospital, Birmingham, UK
The Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK
J. Campos Rheumatology Research Group, Institute of Inflammation and Ageing
(IIA), University of Birmingham, Birmingham, UK
Puran Chen Center for Infectious Medicine, F59, Department of Medicine,
Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm,
Sweden
Joshua D’Rozario Department of Biochemistry and Molecular Biology, Monash
University, Clayton, VIC, Australia
Institute of Immunology and Immunotherapy, University of Birmingham,
Birmingham, UK
Alice E. Denton Lymphocyte Signalling and Development, Babraham Institute,
Cambridge, UK
Douglas T. Fearon Cold Spring Harbor Laboratory, Weill Cornell Medical
College, New York, NY, USA
Andrew Filer Rheumatology Research Group, Institute for Inflammation and
Ageing, College of Medical and Dental Sciences, University of Birmingham, Queen
Elizabeth Hospital, Birmingham, UK
Anne Fletcher Department of Biochemistry and Molecular Biology, Monash
University, Clayton, VIC, Australia
Institute of Immunology and Immunotherapy, University of Birmingham,
Birmingham, UK
xi
xii Contributors
Paul M. Kaye Centre for Immunology and Infection, Department of Biology and
Hull York Medical School, University of York, York, UK
Konstantin Knoblich Department of Biochemistry and Molecular Biology,
Monash University, Clayton, VIC, Australia
Institute of Immunology and Immunotherapy, University of Birmingham,
Birmingham, UK
Helen M. McGettrick Rheumatology Research Group, Institute of Inflammation
and Ageing, University of Birmingham, Birmingham, UK
C. G. Mueller CNRS UPR 3572, Laboratory of Immunopathology and Therapeutic
Chemistry/Laboratory of Excellence MEDALIS, Institut de Biologie Moléculaire et
Cellulaire, Université de Strasbourg, Strasbourg, France
Hafsa Munir MRC Cancer Unit/Hutchison, University of Cambridge, Cambridge,
UK
S. Nayar Rheumatology Research Group, Institute of Inflammation and Ageing
(IIA), University of Birmingham, Birmingham, UK
Amy J. Naylor Rheumatology Research Group, Institute for Inflammation and
Ageing, College of Medical and Dental Sciences, University of Birmingham, Queen
Elizabeth Hospital, Birmingham, UK
Iryna V. Pinchuk Departments of Internal Medicine, University of Texas Medical
Branch, Galveston, TX, USA
Microbiology and Immunology, University of Texas Medical Branch, Galveston,
TX, USA
Don W. Powell Departments of Internal Medicine, University of Texas Medical
Branch, Galveston, TX, USA
Neuroscience, Cell Biology and Anatomy, University of Texas Medical Branch,
Galveston, TX, USA
David Roberts Institute of Immunology and Immunotherapy, University of
Birmingham, Birmingham, UK
Edward W. Roberts Department of Pathology, University of California San
Francisco, San Francisco, CA, USA
Muath Suliman Institute of Immunology and Immunotherapy, University of
Birmingham, Birmingham, UK
Mattias Svensson Center for Infectious Medicine, F59, Department of Medicine,
Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm,
Sweden
