Chapter 1 - Introduction

Abstract

Immunological thought is exerting a growing effect in cancer research, correcting a divorce that occurred in the mainstream of the field decades ago as cancer genetics began to emerge as a dominant movement. During the past decade, a new general consensus has emerged among all cancer researchers that inflammation and immune escape play crucial causal roles in the development and progression of malignancy. This consensus is now driving a new synthesis of thought with great implications for cancer treatments of the future. This book introduces new concepts and practices that will dramatically affect oncology by adding new immune modalities to present standards of care in surgery, radiotherapy and chemotherapy. Its aim is to cross-fertilize ideas in the new area of immunochemotherapy, which strives to develop new combinations of immunological and pharmacological agents as cancer therapeutics. Specifically, our goals are to (1) highlight novel principles of immune suppression in cancer, which represent the major salient breakthroughs in the field of cancer immunology the last decade, and to (2) discuss the latest thinking in how immunotherapeutic and chemotherapeutic agents might be combined, not only to defeat mechanisms of tumoral immune suppression but also to reprogram the inflammatory microenvironment of tumor cells to enhance the long-term outcomes of clinical intervention. Many immune-based therapies have focused on activating the immune system. However, it is now clear that these therapies are often thwarted by the ability of cancers to erect barricades that evade or suppress the immune system. Mechanistic insights into these barricades have enormous medical implications, not only to treat cancer but also many chronic infectious and age-associated diseases where relieving pathogenic immune tolerance is a key challenge. In this book, contributors with a wide diversity of perspectives and experience provide an introductory overview to the immune system; how tumors evolve to evade the immune system; the nature of various approaches used presently to treat cancer in the oncology clinic; and how these approaches might be enhanced by inhibiting important mechanisms of tumoral immune tolerance and suppression. The overarching aim of this treatise is to provide a conceptual foundation to create a more effective all-out attack on cancer. This chapter offers a historical perspective on the development of immunological thought in cancer, a discussion of some of the fundamental challenges to be faced, and an overview of the chapters which frame and address these challenges.