Analyzing T cell responses

Abstract

This book represents the first comprehensive description and evaluation of the most important assays utilized to monitor immune responses against tumor associated antigens. Each chapter, prepared by leading investigators in tumor immunology and immunotherapy, details a specific immune topic or analytical method. Specifically tailored to the needs of clinical researchers, basic science investigators, and biotechnology innovators, this book provides information that is both sufficiently detailed and eloquently succinct. All discussions are substantiated with a comprehensive literature review. The categorization and organization of these sections is such that one can either pursue the entire book or quickly find necessary information on a specific assay or concept of interest. An in-depth description of the methods utilized in the identification of tumor associated antigens is complemented by extensive lists of HLA class I and class II restricted antigens. This book also addresses the essential topic of tumor cells’ ability to evade immune recognition and destruction. The potential mechanisms regarding the disparity between the patients’ immunological and clinical response following immunization are reviewed. Importantly, potential therapeutic strategies to overcome the immune escape mechanisms have been discussed. Having described an appropriate amount of background information in order to establish a fundamental understanding of the antigen-specific immune responses, the book then moves to specifically address the particular assays utilized by the tumor immunologists in the following chapters: Cytotoxicity Assays focuses on evaluating the cellular immune responses to tumors and the monitoring of killer lymphocytes in cancer patients. In addition, the killing mechanisms utilized by the effector lymphocytes and the different types of CTL-inducing cancer vaccines are discussed. Monitoring T Cell Proliferation highlights the importance of proliferation as a significant indicator of lymphocyte activation. Specifically, important regulators and principles of T cell proliferation are reviewed. A variety of monitoring techniques and methods for data analysis are also discussed. ELISPOT Assay concentrates on the principle, performance, result interpretation and limitations of this important and widely used method for monitoring the immune status of patients receiving cancer vaccines. A very helpful section on the assay’s problems and suggested solutions is also included. Modified ELISPOT describes some modifications of this assay specifically developed for T cell monitoring in cancer vaccine trials. These modifications, Granzyme B ELISPOT and Autologous Tumor IFN-γ ELISPOT, allow better assessment of low frequency tumor-specific CTL and their functions in cancer vaccine trials. Intracellular Cytokine Staining focuses on the technique of this sensitive assay for analysis of T cell responses. In addition, monitoring of spontaneous tumor immunity and vaccination studies in patients with cancer are also discussed. Cytometric Cytokine Secretion Assay provides a detailed description of this innovative method for the analysis and enrichment of viable cells according to the secreted cytokines. The cytokine secretion assay has proven to be especially useful for the detection and isolation of viable antigen-specific T cells after a short restimulation with specific antigen in vitro to induce secretion of cytokines. This chapter provides comprehensive background information and very useful practical considerations on the detection and isolation of cytokine-secreting, antigenspecific T cells. Cancer Metastasis Rev (2006) 25:501–502 DOI 10.1007/s10555-006-9015-1