Melanoma, Darwinian medicine and the inner world

• Published in: Journal of cancer research and clinical oncology Vol. 136; no. 12; pp. 1787 - 1794
• Main Authors: Krone, B, Grange, J. M
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.12.2010; Springer-Verlag; Springer; Springer Nature B.V
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Cancer Research; Cancer Vaccines - administration & dosage; Cancer Vaccines - immunology; CD8-Positive T-Lymphocytes - immunology; Dermatology; Endogenous Retroviruses - genetics; Epidemiology. Vaccinations; Gene expression; General aspects; Genome, Human - genetics; Hematology; HERV; Humans; Hygiene hypothesis; Immune repair; Immune system; Immune System - immunology; Infectious diseases; Internal Medicine; Koch postulates; Medical sciences; Medicine; Medicine & Public Health; melanoma; Melanoma - genetics; Melanoma - immunology; Melanoma - prevention & control; Oncology; Pathology; Pharmacology. Drug treatments; Proviruses - genetics; Review; Skin cancer; Tumors of the skin and soft tissue. Premalignant lesions; Viruses; World; HERV; Hygiene hypothesis; Immune repair; Koch postulates; Melanoma; Malignant tumor; Hypothesis; Medicine; Malignant melanoma; Repair; Hygiene; Cancer; International
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-010-0949-x

Introduction A diverse range of human diseases, including allergy, asthma, autoimmune disease, cancer and chronic neurologic diseases, notably multiple sclerosis and endogenous depression, is becoming more prevalent in industrialized countries. It has been postulated that environmental factors associated with improved standards of hygiene play a leading role in this process since the immune system seems to need extrinsic challenges for its proper maturation. The inner world An added dimension has now emerged—the impact on disease of the inner world, principally the numerous endogenous retroviruses (HERVs) within the human genome. Taking melanoma as an example, we propose a framework for understanding how a complex infectious and immunological background can induce or inhibit expression of a HERV-related disease process. The central role of a failure to induce or to maintain certain populations of self-specific CD8⁺ T-cells mediating immune surveillance, the expression of HERV-encoded peptides on affected cells and pathological mechanisms directly attributable to HERV proteins are discussed. Conclusions The presented concepts explain events preceding the clinical manifestation of diseases by several years and provide a rationale for the use of currently available vaccines to protect against certain HERV-induced diseases, especially melanoma. Criteria for establishing the causal role of HERVs in a given disease are proposed.