Cancer Immune Therapy Edited by G. Stuhler and P. Walden ...

224 10 The Immune System in Cancer: If It Isn't Broken, Can We Fix It?
FOREIGN antigens. Cells infected by invading pathogens express proteins from the
pathogen. Processing of these foreign antigens usually yields epitopes which are distinct
from self epitopes.
Immunological danger signals. Antigens must be presented in the appropriate context
of a highly immunostimulatory environment (the key component of which are
proinflammatory cytokines) to recruit APC and, critically, to activate them to express
high levels of co-stimulatory molecules. Molecules that initiate the creation of this
immunostimulatory environment may be referred to as danger signals [37, 60, 66,
69±71].
Molecular mimicry. Processed epitopes of different proteins may resemble each other
in amino acid sequence sufficiently that, when bound to the same MHC molecule, a
single TCR will recognize either complex and become activated. The activated T cells
will then recognize cells expressing either of the two proteins (see Fig. 10.3).
NEAR-SELF tumor antigens. Some cellular proteins in a cancer cell will be mutated.
Epitopes derived from the mutated parts of these antigens will have a different structure
from those epitopes derived from the normal cellular counterparts and so there
are likely to be only a few T cells with TCR which have the fine structure to distinguish
a self from a near-self epitope.
SELF antigens. Normal (unmutated) cellular antigens. Generally no, or very few, T
cells exist that recognize them.
Subdominant epitopes. Following vaccination with a given antigen, the majority of the
T cell response (at least initially) will be directed against only one, or a few, dominant
epitopes derived from that antigen. The remaining minority of the reactive T cells
will recognize other subdominant epitopes. The nature of an epitope as dominant or
subdominant will be determined by a variety of factors, including the affinity with
which the epitope binds to MHC molecules and its interactions with other components
of the antigen-presenting pathway.
Tumor antigen. Any cellular antigen that is expressed exclusively or predominantly by
tumor cells. Epitopes from tumor antigens have the potential to stimulate tumorspecific
immune reactivity, provided T cells with appropriate TCR exist to recognize
them.