Cancer Immunotherapy at the Crossroads: How Tumors Evade Immunity and What Can Be Done (Current Clinical Oncology)

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. Front Matter....Pages i-xvii Front Matter....Pages 1-1 HLA Class I Antigen-Processing Machinery and HLA Class I Antigen-Derived Peptide-Complex Defects in Tumor-Cell Escape....Pages 3-34 Immune Defects in T Cells From Cancer Patients....Pages 35-48 Malfunction of the Dendritic Cell System in Cancer....Pages 49-65 CD4+ T-Cell-Mediated Immunity to Cancer....Pages 67-86 Immunological Ignorance in Cancer....Pages 87-99 The Role of Receptor-Mediated Apoptosis in T-Cell Dysfunction....Pages 101-117 Alterations in T-Cell Signaling Pathways and Increased Sensitivity to Apoptosis....Pages 119-144 The Role of Tumor Gangliosides in the Immune Dysfunction of Cancer....Pages 145-156 Interleukin-10-Induced Immune Suppression in Cancer....Pages 157-172 Accentuating Tumor Immunity Through Costimulation....Pages 173-194 Optimizing T-Cell Adoptive Immunotherapy to Overcome Tumor Evasion....Pages 195-213 Tumor Resistance to Apoptosis....Pages 215-234 Front Matter....Pages 235-235 The Development and Reversal of T-Cell Tolerance in Cancer Patients Receiving Peptide-Based Vaccines....Pages 237-255 Altered Signaling in T Lymphocytes of Patients With Cancer....Pages 257-277 Allogeneic Hematopoietic Blood-Cell Transplantation As Immunotherapy for Metastatic Renal Cell Carcinoma....Pages 279-293 Immune Defects in Patients Suffering From Non-Hodgkin’s Lymphoma....Pages 295-314 Immune Dysfunction in Classical Hodgkin’s Lymphoma....Pages 315-334 Lung Cancer and Immune Dysfunction....Pages 335-350 Primary Malignant Brain Tumors....Pages 351-371 Back Matter....Pages 373-386 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 these immune functions may be protected or restored in order to more effectively support the process of tumor rejection in situ. Cutting-edge techniques are outlined 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.