Innate Immune Regulation And Cancer Immunotherapy

Innate and adaptive immunity play important roles in immunosurveillance and tumor destruction. However, increasing evidence suggests that tumor-infiltrating immune cells may have a dual function: inhibiting or promoting tumor growth and progression. Although regulatory T (Treg) cells induce immune tolerance by suppressing host immune responses against self- or non self-antigens, thus playing critical roles in preventing autoimmune diseases, they might inhibit antitumor immunity and promote tumor growth. Recent studies demonstrate that elevated proportions of Treg cells are present in various types of cancers and suppress antitumor immunity. Furthermore, tumor-specific Treg cells can inhibit immune responses only when they are exposed to antigens presented by tumor cells. Therefore, Treg cells at tumor sites have detrimental effects on immunotherapy directed to cancer.

This volume is edited by Dr. Sudhir Gupta, internationally recognized expert in Immunology, Professor of Medicine, Pathology, Microbiology and Molecular Genetics. Topics include toll receptors, dendritic cells, NK cells, and complement receptors.

The interplay of innate and adaptive antitumor immunity dictates the intensity and outcome of the endogenous anticancer response. Stress-induced molecules on tumor cells trigger innate immune reactions, whereas the processing and presentation of tumor-associated antigens evokes adaptive immune recognition. Innate and adaptive antitumor responses may impact tumor development in different ways. In some cases, endogenous reactions suppress tumor formation, while exerting a selective pressure that fosters the emergence of escape variants. Alternatively, some host responses promote tumor cell growth, invasion, and metastasis through the elaboration of inflammatory mediators and cytokines. Investigations have uncovered unique and overlapping roles for innate and adaptive anti tumor immunity, revealing a complex network of interactions among tumor cells, immune elements, and stromal components within the tumor microenvironment, which together shape the direction, quality, and dynamics of the anticancer response.

Once alerted by the innate immune system to the presence of a pathogen or a cellular abnormality, the adaptive immune system responds by activating and expanding antigen-specific B and T lymphocytes. This chapter focuses specifically on the activation and activities of T lymphocytes, which coordinate the adaptive immune response. We open with a description of where and how naïve T cells first encounter antigen. We then examine what factors influence the differentiation of helper CD4+ T lymphocytes into one of several effector subsets, each of which secretes a distinct subset of cytokines. We follow with a discussion of the origin and function of cytotoxic CD8+ T cells, the lymphocyte with the capacity to directly kill tumor cells. We close with a brief summary of the unique challenges that face the adaptive immune system when it tried to mount a response to a tumor.

Patients are beginning to benefit from antibody based, cellular and vaccine approaches that are effective against genetically diverse and therapy-resistance cancers. BCG immunotherapy is now being used as a first line treatment for human bladder cancer and the introduction of prophylactic vaccination against Hepatitis B and HPV cancers is starting to show positive results. Following recent FDA approval for a vaccination against prostate cancer, and optimistic results in clinical trials for a vaccine targeting cancer antigens in lung cancer, cancer immunotherapy is now significantly impacting patient clinical management. Tumor Immunology and Immunotherapy provides an up-to-date and comprehensive account of cancer immunity and immunotherapy. It discusses our adaptive and innate immunity to cancer, the mechanisms underpinning our immune response, current approaches to cancer immunotherapy, and how tumour and host responses can circumvent effective anti-cancer immunity. The book examines recent results, publications and current areas of interest including 'immune editing' and the specific issues that are affecting the research and development of vaccines, providing insight into how these problems may be overcome, as viewed by world leaders in the field. Tumor Immunology and Immunotherapy will appeal to clinicians working in oncology and cancer immunotherapy, and research scientists including PhD and masters students, post-doctoral researchers and senior investigators.