Book Review

Cancer Immunotherapy: Immune Suppression and Tumor Growth

N Engl J Med 2008; 358:1764-1765April 17, 2008

Article

Cancer Immunotherapy: Immune Suppression and Tumor Growth
Edited by George C. Prendergast and Elizabeth M. Jaffee. 409 pp., illustrated. San Diego, CA, Elsevier Academic Press, 2007. $99.95. ISBN: 978-0-12-372551-6

The successful manipulation of a cancer-directed immune response has long been a goal of cancer immunologists. Occasionally, spectacular successes have reinforced the enthusiasm of some investigators for this goal, but the more common failed attempts to manipulate the immune response have led many to conclude that other treatments will be more productive. These polarized views have been tempered by recent advances in the understanding of the elements and regulation of the immune response, and by the definition of how cancers evade immune recognition and disarm, divert, or destroy immune effector mechanisms. Many authorities believe that new treatment strategies that address tumor-derived immunosuppression will be productive and that now is a good time to review the status of work in this area.

This relatively compact book is a summary of contemporary thinking about cancer immunotherapy, with a focus on the relationship between tumors and the immune response of the host. The book is edited by authorities on tumor biology and cancer immunotherapy and reflects the nascent synthesis of these disciplines. The chapters are written by highly respected investigators, and the topics span much of the breadth and depth of this evolving field.

The book seems designed to provide an overview for those who wish to immerse themselves in this field and who have a working knowledge of immunology but rudimentary familiarity with cancer immunobiology and therapy. The first part of the book reviews the principles of cancer immunobiology. These six chapters cover a considerable amount of territory that will be redundant for experts but useful for novices. The chapter on cancer immunoediting, contributed by Ryungsa Kim, provides a clear overview of this important concept, though it would have been better if the first chapter of the book were more focused on the clinical evidence supporting or refuting the role of the immune response in cancer biology. There is a fair amount of redundancy in this section, as might be expected, but this should be reinforcing and not distracting for most readers.

The second part of the book emphasizes cancer therapeutics. Although these five chapters will be useful for the uninitiated, they will add little knowledge or perspective for many readers, who will find that many other reference sources are more useful. This part of the book would have benefited from more systematic attempts to define how chemotherapy and targeted therapeutics may influence the evolution of antitumor immune responses.

The weaknesses in the second section are substantially erased by the third and final part of the book, which addresses targets and tactics for improving cancer immunotherapy by defeating immune suppression. This section is timely, important, and of potential value to any reader who wishes to learn more about this rapidly evolving and intensely translational field of research. The chapter on partnering immunotherapy and other cancer therapeutics, written by Leisha Emens and Elizabeth Jaffee, is particularly useful, as is the chapter on immune stimulatory features of classical chemotherapy, written by Robbert van der Most, Anna Nowak, and Richard Lake.

The other chapters in this section are uniformly exemplary, and they describe a wide range of immunosuppressive mechanisms, including immune checkpoint activation, regulatory T-cell induction, tumor-associated macrophages, tumor-associated myeloid suppressive cells, and biochemical modulators such as indoleamine 2,3-dioxygenase, arginase, and nitric oxide synthase. The identification and characterization of each of these mechanisms provide opportunities to develop specific mechanism-directed inhibitors that can release the brakes on tumor-derived immunosuppression.

As might be expected from any concise volume, there are gaps in the subject matter. For example, there are no chapters dedicated to monoclonal antibody therapy, even though such treatments have emerged as critically important elements of cancer therapy. Although it could be argued that many antibodies act through nonimmune mechanisms, it is clear that this is not always the case. Moreover, a large number of immunomodulatory antibodies are in various stages of clinical development, and many of these approaches are specifically designed to defeat aspects of tumor-derived immunosuppression. There is no chapter devoted to adoptive cellular therapy, even though many of these approaches specifically address tumor-derived immunosuppression.

The book would have benefited from a thorough discussion of challenges and accomplishments in the area of immune monitoring to assess biomarkers of response. Finally, it would have been timely and valuable to include some content regarding vaccines that prevent cancer by preventing infections (e.g., hepatitis B and human papillomavirus) because the underlying principles of efficacy are undoubtedly relevant to future immunotherapy applications. However, these criticisms do not substantially detract from a book that will prove useful as an introduction to the rapidly evolving field of cancer immunotherapy with a focus on overcoming tumor-derived immunosuppression.

Louis M. Weiner, M.D.
Georgetown University Medical Center, Washington, DC 20057
weinerl@georgetown.edu