The Role Of Tumor Associated Macrophages In Tumor Progression

This volume examines in detail the role of chronic inflammatory processes in the development of several types of cancer. Leading experts describe the latest results of molecular and cellular research on infection, cancer-related inflammation and tumorigenesis. Further, the clinical significance of these findings in preventing cancer progression and approaches to treating the diseases are discussed. Individual chapters cover cancer of the lung, colon, breast, brain, head and neck, pancreas, prostate, bladder, kidney, liver, cervix and skin as well as gastric cancer, sarcoma, lymphoma, leukemia and multiple myeloma.

The subject of Tumour-Associated Macrophages is of interest in the cancer research community, and this book promises to be among the first to discuss a definitive theory on the role of macrophage in tumor development.

Tumor development and progression are strongly linked to inflammation and macrophage infiltration is a major component of the inflammatory reactions associated with neoplasia. Plasticity is a hallmark of mononuclear phagocytes, which undergo polarized diverse forms of activation. Metabolic adaptation is a key component of macrophage plasticity and polarization, instrumental to their function in homeostasis, immunity and inflammation. Tumor-associated macrophages (TAM) and related immature myeloid suppressor cells generally have properties of an M2-like population. TAM produce growth factors, have immunoregulatory and immunosuppressive activity, stimulate angiogenesis and provide tissue remodeling, invasion and metastasis. Thus, TAM are a key component of cancer-promoting inflammatory reactions.

This volume – for pharmacologists, systems biologists, philosophers and historians of medicine – points to investigate new avenues in pharmacology research, by providing a full assessment of the premises underlying a radical shift in the pharmacology paradigm. The pharmaceutical industry is currently facing unparalleled challenges in developing innovative drugs. While drug-developing scientists in the 1990s mostly welcomed the transformation into a target-based approach, two decades of experience shows that this model is failing to boost both drug discovery and efficiency. Selected targets were often not druggable and with poor disease linkage, leading to either high toxicity or poor efficacy. Therefore, a profound rethinking of the current paradigm is needed. Advances in systems biology are revealing a phenotypic robustness and a network structure that strongly suggest that exquisitely selective compounds, compared with multitarget drugs, may exhibit lower than desired clinical efficacy. This appreciation of the role of polypharmacology has significant implications for tackling the two major sources of attrition in drug development, efficacy and toxicity. Integrating network biology and polypharmacology holds the promise of expanding the current opportunity space for druggable targets.

A link between inflammation and cancer has been established many years ago, yet it is only recently that the potential significance of this connection has become apparent. Although several examples of chronic inflammatory conditions, often induced by persistent irritation and/or infection, developing into cancer have been known for some time, there has been a notable resistance to contemplate the possibility that this association may apply in a causative way to other cancers. Examples for such progression from chronic inflammation to cancer are colon carcinoma developing with increased frequency in patients with ulcerative colitis, and the increased incidence of bladder cancer in patients suffering from chronic Schistosoma infection. Inflammation and cancer have been recognized to be linked in another context for many years, i.e., with regards to pathologies resembling chronic lacerations or 'wounds that do not heal.' More recently, the immunology of wound healing has given us clues as to the mechanistic link between inflammation and cancer, in as much as wounds and chronic inflammation turn off local cell-mediated immune responses and switch on growth factor release as well the growth of new blood vessels - angiogenesis. Both of these are features of most types of tumours, which suggest that tumours may require an immunologically shielded milieu and a growth factor-rich environment.

Tumor immunology and immunotherapy provides a comprehensive account of cancer immunity and immunotherapy. Examining recent results, current areas of interest and the specific issues that are affecting the research and development of vaccines, this book provides insight into how these problems may be overcome as viewed by leaders in the field.

This book is a collection of chapters that discuss methodologies, resources, and technologies by dedicated authors. This book has addressed the significance of macrophages in infectious disease, tumor metabolism, and muscular disorders. All chapters have focused on the fate of differentiated macrophages and discussed molecular pathways that are important for the pathologic role of macrophages. I am confident that our readers will find this book useful in designing immune mediated strategies for managing various diseases that this book is based on.