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

208 10 The Immune System in Cancer: If It Isn't Broken, Can We Fix It?
Fig. 10.2 How immune selection might determine the range of mutations
that are clinically observed in oncoproteins. (A) A wild-type protein
involved in control of cell growth/differentiation is a self antigen that is
invisible to the immune system because there are no T cells with TCR
specificity to any of the antigenic epitopes derived from it. (B) Hypermutation
of this protein would lead to loss of function, so the protein
would be non-transforming and highly immunogenic. (C) A smaller
number of defined mutations might make the protein optimally oncogenic.
These mutations would generate a significant number of foreign
epitopes that would be recognized by circulating T cells. Therefore, cells
containing these proteins would be rejected by the immune system.
(D) A protein containing a minimal number of mutations might be less
transforming but would generate epitopes that were so weakly recognized
(if at all) by peripheral T cells that the protein would be oncogenic but invisible
to the immune system. Cells carrying such mutations would survive
immune-selection and contribute to cancer etiology. This model
might explain in part why many transforming mutations in human cancers
are very subtle.