Editorial [Hot Topic: Tumor Immunology (Guest Editors: Bharat H. Joshi and Raj K. Puri)]

Considerable progress has been made in our understanding of host immune responses to cancer. This includes identification of antigens overexpressed on human tumors and antigen epitopes recognized by the cellular arm of the immune system (CD4+, CD8+ T and NK T-cell populations); identification and characterization of antigen presenting cells (e.g., dendritic cells); co-stimulatory requirements for effective antigen presentation; the role of various cytokines and their receptors in regulating immune responses; understanding of signal transduction pathways that control T cells and APC differentiation; effector cell function and survival; the role of tumor stroma and inflammation on cancer development and the role of suppressor cells (e.g. T-regulatory cells, myeloid-derived suppressor cells, etc.) in tumor development and evading the immune system. The literature contains reports on large number of cancer vaccines and immunotherapy approaches based on the above concepts that are being tested in pre-clinical and clinical trials to treat cancer. This special issue of the journal covers the latest advances in the field of cancer immunology and immunotherapy and discusses host responses against tumors. In the first chapter Berzofsky and Terabe discuss two different types of NKT cells that counter-regulate each other in cancer and form a new immunoregulatory axis. The balance along this axis could modulate immunity to tumors, infections, autoimmune diseases and responses to cancer vaccines. In the second chapter, Petrausch and colleagues elegantly describe the role of regulatory T cells in regulating immunity to self, allo-antigens, infectious agents, the fetus and cancer. T-regs can suppress the immune response by suppression of effector T cell function, antigen-specific priming of naive T cells or modulation of the function of antigen-presenting cells. These authors describe strategies for modulating and eliminating T-regs in the context of cancer vaccines. In the third chapter, Voskens and colleagues discuss important aspects of peptide vaccination offer strategies to enhance success and summarize aspects of CD4+ T cell help in peptide-based cancer vaccine strategies. They also discuss potential strategies to improve peptide based cancer vaccines through the generation of both HLA class I and class II vaccine-specific immune responses. The fourth and fifth chapters cover the role of tumor vascular endothelial cells and VEGF, which is a prominent tumor cytokine that manipulates both angiogenesis and tumor immunity to enhance tumor survival. Varney et al. discuss involvement of the tumor microenvironment and production of inhibitory factors such as VEGF-c in tumor angiogenesis and lymphangiogenesis. Johnson et al. describe the emerging role of VEGF in the immune system as well as how therapy directed against VEGF may target multiple aspects of cancer immunology. Methods to inhibit tumor induced angiogenesis, when combined with other approaches, may be a powerful strategy for cancer therapy. Chapters six and seven focus on potent antigen-presenting cells, e.g., dendritic cells. Srivastava and Khar review a pivotal role of DC to attract lymphocytes to control immunological homeostatis through specific receptors. In addition to their antigen presentation functions, these receptors are also believed to induce direct cytotoxicity. Murthy et al. review clinical considerations for the development of dendritic cell-based cancer vaccine protocols. These authors recommend following common standards for monitoring and reporting of DC-based clinical trials to fully realize the potential of this approach. In chapter eight, Puri et al. review the identification and characterization of the TH2 cytokine IL-4 receptor in a variety of human cancers as a tumor antigen and a target for receptor-directed anti-cancer therapy. These authors discuss targeting of IL-4 receptors with a cytotoxin that consists of circularly permuted IL-4 and truncated Pseudomonas exotoxin. Three completed phase 1/ 2 clinical trials of this cytotoxin are summarized. In chapter nine, Strober et al. review their elegant work on the IL-4-related cytokine, IL-13, and the role of high affinity IL-13 receptor (IL-13Rα2) in the development of gastrointestinal fibrosis and cancer surveillance. They demonstrate for the first time that IL-13 can signal through IL-13Rα2 involving the AP-1 pathway and induce TGF-β1 production leading to fibrosis.