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TUMOR
MICROENVIRONMENT AND
MYELOMONOCYTIC CELLS
Edited by Subhra K. Biswas
Tumor Microenvironment and Myelomonocytic Cells
Edited by Subhra K. Biswas
Published by InTech
Janeza Trdine 9, 51000 Rijeka, Croatia
Copyright © 2012 InTech
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Publishing Process Manager Maja Jukic
Technical Editor Teodora Smiljanic
Cover Designer InTech Design Team
First published March, 2012
Printed in Croatia
A free online edition of this book is available at www.intechopen.com
Additional hard copies can be obtained from orders@intechopen.com
Tumor Microenvironment and Myelomonocytic Cells, Edited by Subhra K. Biswas
p. cm.
ISBN 978-953-51-0439-1
Contents
Preface IX
Part 1 Myelomonocytic Cells – Phenotypic and
Functional Diversity in Tumor Microenvironment 1
Chapter 1 Cell Lineage Commitment and
Tumor Microenvironment as Determinants for
Tumor-Associated Myelomonocytic Cells Plasticity 3
Raffaella Bonecchi, Benedetta Savino,
Matthieu Pesant and Massimo Locati
Chapter 2 Functions of Diverse Myeloid
Cells in the Tumor Micro-Environment 17
A. Sica, C. Porta, E. Riboldi, M. Erreni and P. Allavena
Chapter 3 Monocyte Subsets and Their Role in Tumor Progression 43
Andrea I. Doseff and Arti Parihar
Chapter 4 Myeloid Derived Suppressor Cells: Subsets,
Expansion, and Role in Cancer Progression 63
Liang Zhi, Benjamin Toh and Jean-Pierre Abastado
Chapter 5 The Role of Hypoxia in Re-Educating
Macrophages in the Tumour Environment 89
Reuben J. Harwood, Claire E. Lewis and Subhra K. Biswas
Chapter 6 Tumor Inflammatory
Microenvironment in EMT and Metastasis 111
Tingting Yuan, Yadi Wu and Binhua P. Zhou
Part 2 Tumor Microenvironment and Myelomonocytic
Cell Interaction in Specific Cancer Subtypes 135
Chapter 7 Lung Tumor
Microenvironment and Myelomonocytic Cells 137
Minu K. Srivastava, Åsa Andersson, Li Zhu, Marni Harris-White,
Jay M. Lee, Steven Dubinett and Sherven Sharma
VI Contents
Chapter 8 Immunobiology of
Monocytes/Macrophages in Hepatocellular Carcinoma 157
Dong-Ming Kuang and Limin Zheng
Chapter 9 Macrophages and Microglia in Brain Malignancies 173
Cristina Riccadonna and Paul R. Walker
Chapter 10 The Role of Tumor Microenvironment in Oral Cancer 201
Masakatsu Fukuda, Yoshihiro Ohmori and Hideaki Sakashita
Part 3 Regulation of Tumor
Microenvironment – New Players and Approaches 219
Chapter 11 Modulation of Cancer Progression by Tumor
Microenvironmental Leukocyte-Expressed microRNAs 221
Lorenzo F. Sempere and Jose R. Conejo-Garcia
Chapter 12 The Role of Mesenchymal Stem Cells
in the Tumor Microenvironment 255
Aline M. Betancourt and Ruth S. Waterman
Chapter 13 Visualisation of Myelomonocytic Cells in Tumors 287
Tatyana Chtanova and Lai Guan Ng
Preface
Tumor microenvironment represents an extremely dynamic and diverse milieu
consisting of different cell types (e.g. tumor cells, stromal cells), distinct physico-
chemical stimuli (e.g. low oxygen or hypoxia) and a variety of humoral factors such as
cytokines, chemokines and growth factors. The interplay of these different elements is
crucial to tumor progression. Therefore, investigating the tumor microenvironment
has a direct impact on the understanding of the mechanisms which regulate cancer
progression.
Myelomonocytic cells have emerged as key players in the tumor microenvironment. In
particular, tumor associated macrophages (TAMs) have served as the classical
example of the tumor promoting actions of myelomonocytic cells. These cells
constitute a major proportion of the inflammatory infiltrates associated with most
solid tumors and a link between inflammation and cancer. One of the most direct
evidence for the tumor promoting role of TAMs comes from studies which use
transgenic approach to modulate TAM numbers in murine tumor models where TAM
infiltration has been linked to tumor progression, angiogenesis and metastasis.
Similarly, in many human cancers of the breast, cervix, bladder and prostrate, a high
TAM density positively correlates with poor prognosis. More recently, other
myelomonocytic cell types such as blood monocytes, Tie-2-Expressing Monocytes
(TEMs), Myeloid-Derived Suppressor Cells (MDSCs), and Tumor Associated
Neutrophils (TANs) have been shown to possess protumoral activity. Inspite of these
evidences, several aspects of myelomonocytic cell repertoire in the tumor
microenvironment remains to be understood. For example, the plasticity of these cells
across different phases of cancer progression, the dialogue between these cells and
other lymphocytic populations in the tumor tissues, and the possibility of re-
programming the tumor microenvironment by strategies to modulate myelomonocytic
cells in vivo.
The objective of this book is to present a comprehensive overview of the dynamic
interaction between the tumor microenvironment and the myelomonocytic cells that
leads to cancer progression. The focus is explaining how the tumor microenvironment
polarizes the myelomonocytic cells to favor tumor growth and how these cells, in turn,
contribute to the shaping and maintenance of the tumor microenvironment.
Mechanisms regulating this process at the level of functional phenotypes,
X Preface
cytokine/chemokine circuits and molecular pathways have also been addressed. For
the reader's ease, the book is divided into three broad sections: section 1 introduces
some of the basic features of myelomonocytic cells and details the general functions
and the diversity of these cells in the tumor microenvironment; Section 2 focusses on
describing the tumor microenvironments of specific cancer types, such as brain cancer,
liver cancer, oral cancer, lung cancer and melanoma and the role of myelomonocytic
cells therein; Section 3 focusses on describing some new players (e.g. mesenchymal
stem cells, microRNAs) and novel approaches (e.g. in vivo imaging) of studying the
tumor microenvironments.
In the end, I would like to express my sincere gratitude to Profs Alberto Mantovani,
Antonio Sica and Ajit Sodhi for mentoring me in the field of macrophage research. I
am indebted to Saki, for her constant support and encouragement; to Prof. B. Lahiry
for kindling my curiosity to look into the unknown. I am grateful to all my
collaborators who have contributed to my research and the generous grant support
from Biomedical Research Council (A*STAR). Finally, I would like to thank Maja and
her colleagues at In Tech without whose help the production of this book would not
have taken place.
Subhra K. Biswas, PhD
Principal Investigator
Singapore Immunology Network (SIgN),
Agency for Science, Technology & Research (A*STAR),
8A Biomedical Grove; #04 Immunos,
Singapore
. TUMOR MICROENVIRONMENT AND MYELOMONOCYTIC CELLS Edited by Subhra K. Biswas Tumor Microenvironment and Myelomonocytic Cells Edited by Subhra K. Biswas . this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechopen.com Tumor Microenvironment and Myelomonocytic Cells, Edited by Subhra K. Biswas. Masakatsu Fukuda, Yoshihiro Ohmori and Hideaki Sakashita Part 3 Regulation of Tumor Microenvironment – New Players and Approaches 219 Chapter 11 Modulation of Cancer Progression by Tumor Microenvironmental
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