Cancer is a significant and growing problem worldwide. While this increase may, in part, be attributed to increasing longevity, improved case notifications and risk-enhancing lifestyle (such as smoking, diet and
obesity), hygiene-related factors resulting in immuno-regulatory failure may also play a major role and call for a revision of vaccination strategies to protect against a range of
cancers in addition to
infections.
DISCUSSION: Human endogenous retroviruses (HERVs) are a significant component of a wider family of
retroelements that constitutes part of the human genome. They were originated by the integration of exogenous retroviruses into the human genome millions of years ago. HERVs are estimated to comprise about 8% of human
DNA and are ubiquitous in somatic and germinal tissues.Physiologic and
pathologic processes are influenced by some biologically active HERV families. HERV
antigens are only expressed at low levels by the host, but in circumstances of inappropriate control their genes may initiate or maintain
pathological processes. Although the precise mechanism leading to abnormal HERVs gene expression has yet to be clearly elucidated, environmental factors seem to be involved by influencing the human immune system.HERV-K expression has been detected in different types of
tumors.Among the various human endogenous retroviral families, the K series was the latest acquired by the human species. Probably because of its relatively recent origin, the HERV-K is the most complete and biologically active family.The abnormal expression of HERV-K seemingly triggers
pathological processes leading to
melanoma onset, but also contributes to the morphological and functional cellular modifications implicated in
melanoma maintenance and progression.The HERV-K-MEL
antigen is encoded by a pseudo-gene incorporated in the HERV-K env-gene. HERV-K-MEL is significantly expressed in the majority of dysplastic and normal naevi, as well as other
tumors like
sarcoma,
lymphoma, bladder and
breast cancer. An amino acid sequence similar to HERV-K-MEL, recognized to cause a significant protective effect against
melanoma, is shared by the
antigenic determinants expressed by some
vaccines such as BCG, vaccinia virus and the yellow fever virus.HERV-K are also reactivated in the majority of human breast
cancers. Monoclonal and
single-chain antibodies against the HERV-K
Env protein recently proved capable of blocking the proliferation of human
breast cancer cells in vitro, inhibiting
tumor growth in mice bearing xenograft
tumors.
SUMMARY: A recent epidemiological study provided provisional evidence of how
melanoma risk could possibly be reduced if the yellow fever virus
vaccine (YFV) were received at least 10 years before, possibly preventing
tumor initiation rather than culling
melanoma cells already compromised. Further research is recommended to confirm the temporal pattern of this protection and eliminate/attenuate the potential role of relevant confounders as socio-economic status and other vaccinations.It appears also appropriate to examine the potential protective effect of YFV against other
malignancies expressing high levels of HERV-
K antigens, namely
breast cancer,
sarcoma,
lymphoma and
bladder cancer.Tumor immune-
therapy, as described for the
monoclonal antibodies against
breast cancer, is indeed considered more complex and less advantageous than immune-prevention. Cellular immunity possibly triggered by
vaccines as for YFV might also be involved in anti-
cancer response, in addition to humoral immunity.