IMMUNOLOGY - Roitt A. - Mir 2000

Chapter 20. Tumor Immunology

■ Immunological surveillance, according to theory, ensures the destruction of emerging aberrant Cells by the body's immune system, thereby preventing The Development of most tumors.

■ Immunological surveillance likely acts against Oncogenic Viruses rather than tumors themselves. This is evidenced by the fact that in individuals with immunosuppression, while the overall incidence of tumors increases, in most cases these tumors are associated with oncogenic viruses.

■ Tumor-associated oncogenes elicit a cellular Immune Response. These Antigens are either of viral origin or represent altered or overexpressed products of the body's own genes.

■ Differentiation antigens expressed on tumor cells can be detected using Monoclonal Antibodies. Although these antigens are not restricted to tumor cells, they are useful for Diagnostics and as targets for therapeutic antibody administration.

■ Passive immunotherapy using monoclonal antibodies holds promise if individual cells serve as targets or if antibody penetration into the tumor mass is ensured.

■ Immunotherapy via active immunization or adoptive Cell transfer remains experimental for now. Cytokines are effective against only a few types of tumors.

THE TUMOR AS A TISSUE GRAFT

The notion that tumors can elicit an immune response was proposed long ago. At the beginning of the century, Paul Ehrlich suggested that humans frequently develop "aberrant rudiments"—tumors that would inevitably develop into fatal malignancies unless eliminated by The Immune System. Consequently, the tumor came to be viewed as a Structure analogous to a tissue graft recognized by the immune system. Building upon these concepts, experiments were initiated to stimulate the immune system to reject tumors. Rare cases of spontaneous tumor regression or disappearance following Treatment with bacterial Vaccines (Coley's toxins) were considered evidence of an effective immune response.

Early studies on anti-tumor Immunity (at the turn of the century) showed that transplanted tumors usually regress. This effect was interpreted as a consequence of an immune response. However, this Conclusion was later recognized as invalid for most of such work, as it was established that tumor regression occurred simply due to genetic differences between the host Organism and the tumor tissue. It was only in the post-war years, thanks to the development of genetically homogeneous, inbred strains of rodents, that it became possible to study anti-tumor immune responses in animals per se. Ehrlich's idea of an Immune Response to "aberrant rudiments" was further developed by Burnet and Thomas, who formulated The Theory of immunological surveillance based on it.