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One of the current challenges and failures of immunotherapy is in part due to the complex tumor microenvironment (TME) that provides a formidable barrier to immune infiltration and function. The TME consists of various cell types (tumor cells, fibroblasts, endothelial cells, and immune cells), soluble signaling molecules (cytokines, growth factors, and chemokines), and extracellular matrix. On another note, metabolic disturbances in various TME components, such as hypoxia, acidosis, lactate accumulation, and nutrient deprivation, can play a critical role in the tumor progression. Furthermore, genetic and epigenetic dysfunctions are known to be part of the characteristics of cancer development. The immune cells could have a pro- or anti-tumor role in the TME, and their activity might vary in the context of different cancers. Both innate and adaptive immune cells interact with tumor cells through direct contact or through chemokines and cytokines signaling, shaping the tumor's activity and response to therapy.
Tumor-associated immune cells, in particular myeloid cells, have opposing roles during cancer development by facilitating antitumor immune responses and driving cancer-promoting inflammation. Defective antitumor immunity is prevalent in cancers, and it is now clear that overcoming the myeloid cell-mediated immunosuppressive microenvironment poses tremendous interest for future cancer therapies. JAK/STAT signaling has come to the forefront as a crucial pathway to induce immunosuppression and procancer inflammation. Specifically, STAT3 activation is critical for the phenotype of myeloid cells by regulating immunosuppressive and prometastatic factors, thereby providing myeloid cells with a multitude of tumor-promoting functions. Genetic ablation of STAT3 in the myeloid compartment induces potent innate and adaptive antitumor immunity along with an inhibition of tumor growth and metastasis. Recently, therapeutic targeting of JAK/STAT3 has shown great promise in blocking immunosuppression in preclinical models. One such example is the use of novel siRNA to selectively target STAT3 in myeloid cells, through conjugation to CpG oligonucleotides that agonize Toll receptor TLR9 on myeloid cells. Along with other novel therapeutic strategies to inhibit JAK/STAT signaling, it seems likely that future efforts to target this pathway will be made in single and combination approaches for effective anticancer immunotherapy.
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.
This is an open access book. With a wealth of exciting data emerging in this rapidly evolving field this book will review the state-of-the-art knowledge with emphasis on multidisciplinary decision and management of head and neck cancer. The book provides significant detail on a wide range of topics including: the role of new targets for treatment, immunotherapy, resistance mechanisms, standardizing molecular profiling programs, and new methods to guide therapeutic approaches. In addition different disease situations are addressed including different treatment approaches in primary disease and in recurrent and/or metastatic disease as well as new developments in pathology, surgery and reconstruction techniques, new systemic therapies in salivary gland cancer, and supportive care and follow-up. All disciplines involved in the treatment of head & neck cancer are covered with a focus on translation into daily practice. The 8th-THNO is designed for medical oncologists, head and neck surgeons, radiation oncologists, otolaryngologists, and other medical professionals involved in the treatment of patients with head and neck cancer.
Revealing essential roles of the tumor microenvironment in cancer progression, this book focuses on the role of hematopoietic components of the tumor microenvironment. Further, it teaches readers about the roles of distinct constituents of the tumor microenvironment and how they affect cancer development. Topics include neutrophils, basophils, T helper cells, cytotoxic lymphocytes, fibrocytes, and myeloid-derived suppressor cells, and more. Taken alongside its companion volumes, these books update us on what we know about various aspects of the tumor microenvironment as well as future directions. Tumor Microenvironment: Hematopoietic Cells – Part A is essential reading for advanced cell biology and cancer biology students as well as researchers seeking an update on research in the tumor microenvironment.
This volume presents a snapshot of some of the most important ongoing research in cancer. With cancer as the second leading cause of death worldwide, extensive research is going on globally to decipher the molecular mechanism underlying cancer that will help in finding better targets for drug therapy. The book brings together new research on molecular mechanism and cancer therapeutics in one place. With chapters from experts in their respective fields, chapters cover molecular mechanisms, etiology, prognosis, detection, and treatment of cancer. Emphasis has been given to the intricate mechanism behind the deregulation of cell division, disruption of cell cycle check points, mutation in oncogenes and tumor suppressor genes, apoptosis, and erratic cell signaling. The book discusses in detail topics such as angiogenesis and tumor microenvironment, which are increasingly receiving attention, especially in the field of neoplastic vascularization and metastasis. The book also includes chapters detailing the current understanding and the future perspective of cancer stem cells.
Cancer cells can change and adapt, especially within the host environment; a phenomenon known as cancer plasticity. Several factors, including the immune system can influence, and be influenced by, cancer plasticity which in turn can impact upon patient responses to treatment. As such, we currently face several challenges for implementing combination therapies as effective cancer treatment strategies. We have compiled a topic with a number of articles that emphasize the various aspects of cancer plasticity, describing in particular the important role of the tumor microenvironment. As we embark on a new era of precision medicine with multi-modal therapies for improving patient outcomes, this topic highlights some relevant points for consideration that are pertinent to the incorporation and effective use of new treatments as part of cancer treatment regimens, including immune-modulating drugs.
This book is exceptional in presenting an interdisciplinary approach to the subject of human papillomavirus (HPV) infection in the context of head and neck cancer. Leading experts in the field discuss the epidemiology and molecular biology of HPV-positive head and neck squamous cell carcinoma, HPV testing, the nonsurgical and surgical treatment of HPV-positive tumors, predictive factors for outcome and quality of life, and ongoing trials on the effectiveness of vaccination in disease prevention. It also provides recommendations for testing, diagnosis treatment and vaccination. Otolaryngologists, head and neck surgeons, medical oncologists, radiation oncologists, molecular biologists and pathologists will find this book a valuable resource.