Natural killer (NK) cells are innate lymphoid cells that have a significant role in regulating the defenses against cancer development and certain viral infections. They are equipped with an array of activating and inhibitory receptors that stimulate or diminish NK cell activity, respectively. Inhibitory receptors include, among others, the MHC class I ligands killer cell immunoglobulin-like receptors (KIR) in humans, and members of the Ly49 family of receptors in mice, and CD94/NKG2A. Activating receptors include cytokine and chemokine receptors, and those that interact with ligands expressed on target cells, such as the natural cytotoxicity receptors or NCRs (NKp30, NKp44 and NKp46), NKG2D, CD244 and DNAM-1. In addition, NK cells express Fc?RIIIA or CD16, the receptor that exerts antibody-dependent cell mediated cytotoxicity (ADCC). NK cells also express the death ligands FasL and TRAIL. The killing or sparing of target cells depends on the integration of distinct signals that originate from NK cell receptors. NK cells spare healthy cells that express normal levels of MHC class I molecules and low amounts of stress-induced self-molecules, whereas they kill target cells that down-regulate MHC class I molecules and/or up-regulate stress-induced self-molecules. The latter are common signatures of virus-infected cells and tumors. All the accumulated knowledge on NK cell biology, along with many clinical observations, is driving multiple efforts to improve the arsenal of NK cell-based therapeutic tools in the fight against malignant diseases. Indeed, NK cell-based immunotherapy is becoming a promising approach for the treatment of many cancers. It is well known that NK cells have a significant role in the anti-tumor effect of therapeutic antibodies that use ADCC as a mechanism of action. In addition to this, administration of autologous and allogeneic NK cells after activation and expansion ex vivo is used in the treatment of cancer. Moreover, adoptive transfer of NK cell lines has been tested in humans, and genetically modified NK cells expressing chimeric antigen receptors are being studied in preclinical models for potential use in the clinic.

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.

In this Research Topic, we would like to honor the memory of Prof. Vito Pistoia and pay tribute to his scientific contributions to the field of Cancer Immunity and Immunotherapy. Topic Editor Daniel Olive is the co-founder and shareholder of company Imcheck Therapeutics. All other topic editors declare no competing interests with regards to the Research Topic subject.

Natural killer (NK) cells are innate lymphoid cells that have a significant role in regulating the defenses against cancer development and certain viral infections. They are equipped with an array of activating and inhibitory receptors that stimulate or diminish NK cell activity, respectively. Inhibitory receptors include, among others, the MHC class I ligands killer cell immunoglobulin-like receptors (KIR) in humans, and members of the Ly49 family of receptors in mice, and CD94/NKG2A. Activating receptors include cytokine and chemokine receptors, and those that interact with ligands expressed on target cells, such as the natural cytotoxicity receptors or NCRs (NKp30, NKp44 and NKp46), NKG2D, CD244 and DNAM-1. In addition, NK cells express Fc?RIIIA or CD16, the receptor that exerts antibody-dependent cell mediated cytotoxicity (ADCC). NK cells also express the death ligands FasL and TRAIL. The killing or sparing of target cells depends on the integration of distinct signals that originate from NK cell receptors. NK cells spare healthy cells that express normal levels of MHC class I molecules and low amounts of stress-induced self-molecules, whereas they kill target cells that down-regulate MHC class I molecules and/or up-regulate stress-induced self-molecules. The latter are common signatures of virus-infected cells and tumors. All the accumulated knowledge on NK cell biology, along with many clinical observations, is driving multiple efforts to improve the arsenal of NK cell-based therapeutic tools in the fight against malignant diseases. Indeed, NK cell-based immunotherapy is becoming a promising approach for the treatment of many cancers. It is well known that NK cells have a significant role in the anti-tumor effect of therapeutic antibodies that use ADCC as a mechanism of action. In addition to this, administration of autologous and allogeneic NK cells after activation and expansion ex vivo is used in the treatment of cancer. Moreover, adoptive transfer of NK cell lines has been tested in humans, and genetically modified NK cells expressing chimeric antigen receptors are being studied in preclinical models for potential use in the clinic.

NK Cells in Cancer Immunotherapy: Successes and Challenges explains the latest immunotherapeutic strategies, focusing on NK cells to allow the best and precise combination treatments to cancer patients. The book provides existing background knowledge in the field of immunotherapy and discusses future areas of research required to carry out cutting-edge, validated therapies. Chapters cover advances in immunotherapeutic strategies, in particular, the use of NK cells with and without T-cell therapy in the treatment of cancer. The book is a valuable resource for cancer researchers, oncologists, graduate students and those interested in learning more about novel strategies to treat cancer patients. Immunotherapy is fast becoming the method of choice for cancer therapy. Although remarkable advances have been made in the field of immunotherapy, there are significant challenges and difficulties ahead since many of the current immunotherapeutic strategies do not provide long-lasting treatment strategies, and therefore are not very effective. Covers CAR/T and CAR/NK and adoptive NK cell therapy with and without T cell therapies Discusses basic biology of NK cells and mouse models of human cancers and the role of NK cells in metastatic cancer and in cancer stem cells Encompasses information on combination therapies using check point inhibition, adoptive transfer of cytotoxic effector cells, chemotherapeutic drugs and activating and inhibitory antibodies

Successes and Challenges of NK Immunotherapy: Increasing Anti-tumor Efficacy describes the unique therapeutic applications of NK cells to fight cancers and eliminate the bulk and subset of cancer stem cells responsible for metastasis, relapse and recurrences. The book provides information on the development, engineering, mechanisms of action, response to various preclinical models, and applications in various clinical trials. Sections cover the development of highly engineered cytotoxic NK cells, their mechanisms of action, preclinical and clinical applications, the development and application of CAR-NK cells, and new NK-drug conjugates, also emphasizing that activated NK cells can target and kill highly resistant cancer stem cells. Written by the leading experts on NK immunotherapy worldwide, this is a valuable resource for researchers, clinicians and members of the biomedical field who are interested in understanding novel and efficient therapies to fight cancers. Discusses the unique developmental applications of NK immunotherapy against cancers, which differs greatly from other types of immunotherapies Provides up-to-date and highly relevant information through chapters written by the leading researchers in the field Presents a significant number of schematic diagrams for easy understanding and reproducibility

Natural killer (NK) cells have been at the forefront of immunology for two decades. During that time, a great amount of information about these cells has been obtained. They are important in antiinfectious and antitumoral defense and shape the adaptive immune response. In addition, they can act as immunoregulatory cells. In recent years, the therapeutic potential of NK cells in cancer immunotherapy has become increasingly evident. This book describes in detail current knowledge about NK cells and covers a broad range of NK cell-related topics, including those that are not frequently reviewed, e.g. NK cells and allergy or NK cells and skin diseases.