Cancer Immunotherapy at the Crossroads: How Tumors Evade Immunity and What Can Be Done

Author: James H. Finke
Published: January 2004
Publisher: Humana Press
ISBN: 1588291839
Hardcover Book
Number of Pages: 408

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The growing evidence that tumors can evade the immune system through a variety of mechanisms makes understanding these processes critical to implementing new and more effective forms of immunotherapy. In Cancer Immunotherapy at the Crossroads: How Tumors Evade Immunity and What Can Be Done, leading investigators and clinicians detail the different mechanisms used by tumors to escape and impair the immune system and then spell out possible clinical strategies to prevent or reverse tumor-induced immune dysfunction. The authors review the mechanisms of immune dysfunction and evasion mechanisms in histologically diverse human tumors, focusing on tumor-induced molecular defects in T cells and antigen-presenting cells (dendritic cells and tumors) that may serve as biomarkers for patient prognosis. They discuss the means by which immune functions may be protected or restored in order to more effectively support the process of tumor rejection in situ. Cutting-edge techniques with the capacity to monitor the strength and quality of patients' immune responses using immunocytometry, MHC-peptide tetramers combined with apoptosis assay, ELISPOT assay, and detection of MHC-TAA peptide complexes on tumor cells are also outlined. State-of-the-art and insightful, Cancer Immunotherapy at the Crossroads: How Tumors Evade Immunity and What Can Be Done illuminates the possibilities for developing effective immunotherapies that can block the mechanisms by which tumors evade the immune system in different histologic types of tumors.

Though the immune system is mainly devoted to controlling and eliminating infectious organisms such as pathogenic bacteria and viruses, many studies suggest that with the proper prodding, it can be convinced to attack tumors as well. Research oncologists, immunologists, pathologists, and other medical scientists outline the basic mechanisms that may be operative in cancer patients to contribute to the poor development of anti-tumor immune responses despite the prodding. Then they review the clinical relevance of immune evasion, discussing the functional and signaling defects in T cells and antigen-presenting cells and their relation to impaired anti-tumor immune responses and to poor clinical outcomes.

Table of Contents:

Dedication
Preface
List of Contributors
1 HLA Class I Antigen-Processing Machinery and HLA Class I Antigen-Derived Peptide-Complex Defects in Tumor-Cell Escape 3
2 Immune Defects in T Cells From Cancer Patients: Parallels in Infectious Diseases 35
3 Malfunction of the Dendritic Cell System in Cancer 49
4 CD4+ T-Cell-Mediated Immunity to Cancer 67
5 Immunological Ignorance in Cancer 87
6 The Role of Receptor-Mediated Apoptosis in T-Cell Dysfunction 101
7 Alterations in T-Cell Signaling Pathways and Increased Sensitivity to Apoptosis
8 The Role of Tumor Gangliosides in the Immune Dysfunction of Cancer 145
9 Interleukin-10-Induced Immune Suppression in Cancer 157
10 Accentuating Tumor Immunity Through Costimulation: A Detailed Analysis of OX40 Engagement and CTLA-4 Blockade 173
11 Optimizing T-Cell Adoptive Immunotherapy to Overcome Tumor Evasion 195
12 Tumor Resistance to Apoptosis: Mechanisms of Evasion and Implications for Radiation and Chemotherapeutic Strategies 215
13 The Development and Reversal of T-Cell Tolerance in Cancer Patients Receiving Peptide-Based Vaccines 237
14 Altered Signaling in T Lymphocytes of Patients With Cancer: A Biomarker of Prognosis? 257
15 Allogeneic Hematopoietic Blood-Cell Transplantation as Immunotherapy for Metastatic Renal Cell Carcinoma 279
16 Immune Defects in Patients Suffering From Non-Hodgkin's Lymphoma 295
17 Immune Dysfunction in Classical Hodgkin's Lymphoma 315
18 Lung Cancer and Immune Dysfunction 335
19 Primary Malignant Brain Tumors: Immune Defects and Immune Evasion 351
Index 373

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