Biomedical Engineering Reference
In-Depth Information
of the initial tumor to other sites (Lou and Dean, 2007). Basal cell carcinomas,
although they can be quite invasive, virtually never metastasize and are rarely
fatal. Stem cells, especially certain cells of the neural crest, possess the ability to
migrate through the developing embryo. The neural crest gives rise to the
precursors of melanoma, neuroblastoma, and small cell lung cancers, each of
which is a highly metastatic tumor (Kasemeier-Kulesa et al., 2008). Is the
metastatic tendency of tumor cells related to an innate property of the cancer
stem cells to migrate (Ward and Dirks, 2007)? If so, then the further character-
ization of germ cell migration could lead to new insights into metastasis. Antic-
ancer stem cell therapies might find their best application in the restriction of
metastasis. If metastasis could be prevented, even if the primary tumor remains
intact, then the patient might still experience a substantial increase in survival
time.
4.3 Elimination, Equilibrium, and Escape
In 2001, Shankaran et al. proposed some modifications to the then predomi-
nant theory of immunosurveillance (Shankaran et al., 2001). Later, these were
refined into a hypothesis of ''immunoediting'' (Dunn et al., 2004a,b). The cancer
immunoediting hypothesis proposes that cell-mediated immunosurveillance as
conventionally described takes place, yet envisions three different resulting
outcomes. These are described in the three Es as: elimination wherein the
immune system can eliminate cancer; equilibrium, wherein immunosurveillance
holds an incipient malignancy in check; or escape, wherein the cancer can
escape from the immunosurveillance, often metastasizing. The authors prefer
their paradigm to the use of the older term immunosurveillance, essentially
because their paradigm anticipates opportunities to intervene in each of the
three predicted outcomes of ''immunoediting''. Cancers that inexplicably go
into remission for years provided early evidence for equilibrium. In addition,
there have been a few case reports of organ transplants that have transferred
undetected dormant tumors to the recipients. These provide additional evi-
dence for ''equilibrium''. In this model, chemical carcinogenesis is explained as
the escape of small, latent growths from equilibrium. Evolutionarily, it is
thought that the immune system has not evolved specifically to handle can-
cers, as these are mainly diseases of the post-reproductive elderly. Thus no
selection pressure, per se, has been exerted on the immune responses to
eliminate post-reproductively acquired cell division maladies. The immunoe-
diting hypothesis states that the transformed cell may look like a foreign cell to
the cell-mediated immune response. Cancer cells can then reduce their anti-
genicity by changing the epitopes they show to the immune system so that they
more closely resemble those presented by normal tissue. If tumor cells are
successful in this ''TrojanHorse'' strategy, they enable the final outcome of the
immunoediting theory: escape and metastasis.
