Biomedical Engineering Reference
In-Depth Information
of immunity responsible for destruction of transformed cells remain to be fully characterized.
Both a humoral and cell-mediated response can be induced, although the T-cell response appears
to be the most signifi cant.
Cytotoxic T cells may play a role in inducing direct destruction of cancer cells, in particular
those transformed by viral infection (and who express viral antigen on their surface).
In vitro
studies have shown that cytotoxic T-lymphocytes obtained from the blood of persons suffering
from various cancer types are capable of destroying those cancer cells.
NK cells are capable of effi ciently lysing various cancer cell types and, as already discussed,
IL-2 can stimulate differentiation of NK cells forming LAK cells, which exhibit enhanced
tumouricidal activity. Macrophages, too, probably play a role. Activated macrophages have been
shown to lyse tumour cells
in vitro
, while leaving untransformed cells unaffected. Furthermore,
these cells produce TNF and various other cytokines which can trigger additional immunological
responses. The production of antibodies against tumour antigens (and the subsequent binding of
the antibodies to those antigens) marks the transformed cells for destruction by NK/LAK cells
and macrophages - all of which exhibit receptors capable of binding the F
c
portion of antibodies.
Although immune surveillance is certainly responsible for the detection and eradication of some
transformed cells, the prevalence of cancer indicates that this surveillance is nowhere near 100 per
cent effective. Some transformed cells obviously display characteristics that allow them to evade
this immune surveillance. The exact molecular details of how such 'tumour escape' is achieved
remains to be confi rmed, although several mechanisms have been implicated, including:
•
Most transformed cells do not express class II MHC molecules and express lower than normal
levels of class I MHC molecules. This renders their detection by immune effector cells more
diffi cult. Treatment with cytokines, such as IFN-γ, can induce increased class I MHC expres-
sion, which normally promotes increased tumour cell susceptibility to immune destruction.
•
Transformed cells expressing tumour-specifi c surface antigens that closely resemble normal
surface antigens may not induce an immune response. Furthermore, some tumour antigens,
although not usually expressed in adults, were expressed previously during the neonatal period
(i.e. just after birth) and are thus believed by the immune cells to be 'self'.
•
Some tumours secrete signifi cant quantities of cytokines and additional regulatory molecules
that can suppress local immunological activity. TGF-
(produced by many tumour types), for
example, is capable of inhibiting lymphocyte and macrophage activity.
β
•
Antibody binding to many tumour antigens triggers the immediate loss of the antibody-antigen
complex from the transformed cell surface, either by endocytosis or extracellular shedding.
•
The glycocalyx (carbohydrate-rich outer cell coat) can possibly shield tumour antigens from the
immune system.
Whatever the exact nature of tumour escape, it has been demonstrated, both
in vitro
and
in
vivo
, that immunostimulation can lead to enhanced tumour detection and destruction. Several ap-
proaches to cancer immunotherapy have thus been formulated, many involving application of IL-2
as the primary immunostimulant.
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