Surveillance against tumors--is it mainly immunological?
The concept of tumor surveillance was first formulated by immunologists Mcfarlane Burnet and Lewis Thomas, respectively. They assumed that the immune system would recognize precancerous and cancer cells as non-self and reject them. This concept is only valid for virally transformed cells, however. In humans, EBV, HHV-8, and the papilloma viruses are relevant viral agents in this context. Tumors arising without a contribution by these viruses are regarded by the immune system as "self", with possible rare exceptions like melanoma. Immunological attempts to influence them therefore implies the breaking of tolerance, a much more difficult proposition. Multicellular organisms have powerful surveillance mechanisms of a non-immunological nature against potential neoplastic cells that threaten to disrupt the organism. Four distinct categories can be recognized: (1) DNA repair. Deficiency of repair enzymes may lead to multiple tumors and/or to multicancer syndromes. (2) Epigenetic mechanisms are currently emerging as being capable of modulating the incidence of certain tumors. e.g., by determining the stringency of imprinting and by influencing chromatin structure. (3) Intracellular surveillance. DNA damage, illegitimate activation of oncogenes, and other pathological changes may activate one or several apoptotic pathways. (4) Intercellular surveillance. The tissue microenvironment influences the probability of disseminated tumor cell growth. Moreover, appropriate differentiation inducing signals may revert the tumor cell phenotype.
Klein
George
G
Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden. Georg.Klein@mtc.ki.se
Klein
Eva
E
D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D000957:Antigens, Viral, Tumor / Q000235:genetics / Q000276:immunology*; D002472:Cell Transformation, Viral / Q000235:genetics / Q000276:immunology*; D004263:DNA Tumor Viruses / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007157:Immunologic Surveillance / Q000235:genetics / Q000276:immunology*; D009369:Neoplasms; D017634:Self Tolerance / Q000235:genetics / Q000276:immunology*
D000956:Antigens, Viral; D000957:Antigens, Viral, Tumor