Cancer Immune Therapy Edited by G. Stuhler and P. Walden ...

204 Cancer Immune Therapie: Current and Future Strategies
Edited by G. Stuhler and P. Walden
Copyright # 2002 Wiley-VCH Verlag GmbH & Co. KGaA
ISBNs: 3-527-30441-X (Hardback); 3-527-60079-5
(Electronic)
10
The Immune System in Cancer: If It Isn't Broken, Can We Fix It?
Dragan Terremovic and Richard G. Vile
10.1
Commitment and the Modern Immune System
The importance of immune effector cells in protecting against the emergence of tumors
within immunocompetent hosts has been a point of controversy for many
years. In the 1970s, Burnet proposed that lymphocytes patrol the body and react to,
and remove, tumor cells that have escaped normal controls of growth and differentiation,
giving rise to the concept of ªcancer immunosurveillanceº [1]. However, this
attractive (and comforting) theory became less credible with the observation that
athymic nude mice, lacking functional T cells, develop tumors at the same rate as
their immunocompetent wild-type counterparts. To understand these competing
views better, it is important to realize that immune recognition of tumors is only one
of the roles that the modern immune system has evolved to fulfill. Probably higher
on its list of priorities comes its ability to recognize and respond to invading pathogens.
However, along with this need for vigorous reactivity against non-self antigens,
comes an equally important need to ignore self antigens (see Appendix). Hence, the
modern immune system is constantly pulled in opposite directions with stringent
twin requirements of aggressive responses against infectious foreign pathogens
whilst maintaining a complete lack of response to self antigens to avoid autoimmunity.
Within the confines of these two extremes is the need to deal with the threat posed
by the uncontrolled growth and dissemination of cancer cells. In order to understand
how the immune system should evolve to be able to meet all of the demands that are
asked of it, let us consider the two extreme models (Fig. 10.1). In one model
(Fig. 10.1A), immune recognition of tumors might have become finely tuned to recognize
all emerging tumor cells and the molecular mutations associated with them.
A second option, erring on the side of preventing autoimmune disease, would be an
immune system that has no capacity to respond to emerging tumor cells at all
(Fig. 10.1B). In reality, the most likely situation, which offers maximal benefit to the
species, falls between these two extremes of immunological hypersensitivity and immunological
ignorance (Fig. 10.1).