This book is an ambitious treatise written by an incredibly productive investigator who has lived through the era of the development of immunotherapy. For one who is an interested physician without an extensive background in immunology, the text is an informative history of immunology and immunotherapy. The organization is logical and progressive in scope. There are many useful photographic illustrations, tables, and appendices to augment the narrative, along with 2370 references.
In the first two chapters, Dr. Sinkovics takes the reader through the evolution of the immune system, beginning with rudimentary ancient fusogenic viruses that may have mediated the fusion of prokaryotic and archaeal spheroblasts leading to the formation of the first eukaryotes. We learn about the role of cytokines, heat shock proteins, and other mediators of inflammation that remain well conserved through mammals.
Subsequently, there came lymphocytes and native immunity leading to apoptosis. The role of viral DNA promoting the evolutionary process as well as being the source of oncogenes leading to cancer is explained.
Chapter 2 chronicles the development of the adaptive immune system. The embryologic development of natural killer cells, B cells, T cells, Tregs, and dendritic cells are presented and then put into context within a section on humoral and cell-mediated immunity.
Chapter 3 moves on to cancer vaccines. As the author has lived and worked through the entire era of this body of work, he is in a unique position to put the field into perspective. The various methods to induce or augment a host response to an autologous tumor and the limitations associated with each have led to important lessons.
Dr. Sinkovics cites his frustrations getting the scientific community and granting agencies to accept early work in the field, but perhaps should be forgiven this indulgence. The case is stated that the best use of immunotherapy may be in the treatment of micrometastatic disease after “debulking” surgery as there has been little success treating macroscopic disease, with the exception of some cases of Stage IV melanoma. Particular attention is paid to dendritic cells as antigen-presenting cells for induction of cell-mediated immunity.
Chapter 4 explores the diseases encountered by patients with immune systems that improperly attach normal host tissues, and Chapter 5 details the immune response to pathogenic organisms. Of particular interest is the explanation of the host response to infection with HTLV and HIV.
For one not well-versed in the field, the section on HIV is a thorough yet concise and clear explanation of the origin of the virus and its transmission into humans. Treatment efforts and the emergence of resistant HIV strains are also explained.
The book moves on next to the subject of oncoviruses such as the human papilloma virus and its role in the development of several types of cancer. The author observes that most infections in humans, due to innate and adaptive immunologic defenses, regress. Two prophylactic vaccines to HPV can greatly reduce the risk of development of cervical cancer due to HPV infection.
In Chapter 6, concepts explained earlier come together in a very interesting section, illustrating how RNA regulates gene expression and the viral origins of microRNA. He explains how pathogens and tumors may subvert protective immunologic mechanisms to the detriment of the host. Lastly, the author details the intersection of immunology and oncology, including a discussion of adoptive immunotherapy.
After reading the entire book, we particularly appreciated the summary chapter because the text is often detail laden and, while informative, a bit heavy to read.
The summary recapitulates key concepts and details so that one is left with a clearer understanding of the field. The author does not delve extensively into the mechanics or pathways of the immune system or the interactions of lymphocytes and cytokines, nor does he explore in great detail the progression of clinical trials in immunotherapy. Notable for its absence is an explanation for why immunotherapy seems to be most promising for melanoma and renal cell carcinoma and not other solid tumors.
This text is to be commended particularly for its comprehensive scope and logical organization. This is not only a reference text but a rather a worthwhile historical read written by an investigator who has made significant contributions throughout his long career. We very much enjoyed reading the text and found it interesting, informative, and a masterpiece.