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

210 10 The Immune System in Cancer: If It Isn't Broken, Can We Fix It?
Fig. 10.3 Generation of autoreactive and tumorreactive
responses. If a pathogenic infection is associated
with a protein that resembles a self antigen,
presentation of that antigen by activated DCs
could activate a Tcell that has high affinity for the
pathogenic epitope but retains some affinity for
the self-derived epitope. Activation and prolifera-
tion of this Tcell would induce recognition of cells
infected by the pathogen but also now normal
cells expressing the self peptide on its own MHC
molecules. In addition, if the self peptide is actually
a tumor-associated peptide, these Tcells will
also recognize tumor cells.
have to be presented by dendritic cells (DCs) or other professional antigen-presenting
cells (APCs) in the appropriate context. For optimal immune activation against
an antigen it has to be taken up by an APC within the context of a highly immunostimulatory
(cytokine-rich) environment. This environment both recruits APCs to the
site of antigen release and, critically, activates them. Activation of APCs means that
they not only process and present the epitopes from the antigen, but they also express
high levels of co-stimulatory molecules (see Appendix), such as adhesion molecules
and those of the B7 family. A T cell will only be fully activated to respond to an
epitope if it receives signals from binding the epitope/MHC molecule and additional
co-stimulatory signals provided by binding to these co-stimulatory molecules on the
surface of the activated APCs (see also Fig. 10.4A). Simultaneously, within the target
cells (in our case tumor cells) cellular antigens are continually processed within the
cell and presented as small peptides (8±13 amino acids) in the context of major histocompatibility
complex (MHC) class I molecules. In this way, the immune system
can continually sample the antigenic content of cells through TCR recognition. As
already described, T cells with TCRs which can bind self epitopes bound to MHC
class I molecules have been negatively selected and so will not be present to bind