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

still insufficient to draw definitive conclusions, it appears that mutations and/or dysregulation
can affect each step of the APMs which lead to abnormalities of MHC
class Iand/or IIsurface expression. Regulatory and structural defects appear to affect
the components involved in the biosynthesis of the MHC class Iand IIcomplex
with marked differences. For instance, defects in the regulation of TAP and CIITA
are frequent, whereas sequence alterations in the components have only been rarely
described. In contrast, structural defects appear to occur frequently in the b2-m
gene. Furthermore, it has to be considered that the frequency of mutations in various
components of the MHC class Iand IIAPMs varies significantly among various
types of malignancies. These results suggest that a complete characterization of the
molecular defects underlying abnormalities of the classical MHC class Iand IIAPM
in malignant diseases may suggest strategies to select and monitor patients to be
treated with T cell-based immunotherapies, and to counteract the multiple escape
mechanisms utilized by malignant cells.
The topic of expression of non-classical HLA class Iantigens by malignant cells is in
an early stage. The suggested role of these molecules in the immune escape of tumor
cells is intriguing. However, the available information is still too limited and too
conflicting to draw any conclusions at this time.
Acknowledgments
References 89
We would like to thank J. Bukur (III. Department of Internal medicine, Mainz), Frederico
Garrido and Teresa Cabrera (Granada, Spain) for kindly supplying Figs 5.14,
5.15 (F. G./T. C.) and 5.20 (J. B.), respectively, and I. Schmidt for help in preparing
the manuscript. This work was partially supported by a grant from the Deutsche Forschungsgemeinschaft,
SFB 432, project A5 (B. S.) and the Boehringer Ingelheim
Fond.
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