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

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5 Major Histocompatibility Complex Modulation and Loss
paradox can be explained by the fact that a substantial number of MHC class II surface
molecules are occupied by the non-immunogenic CLIP in HRS cells. This results
in defective loading of these molecules with antigenic peptides and represents
a further mechanism by which tumor cells can evade the immune system [97].
The impact of deficient HLA-DM expression on MHC class II antigen expression
and peptide loading clearly depends on the MHC class II phenotype of the host.
MHC class II + ,Ii ± ,DM ± tumor cells present a broader range of endogenous epitopes
than MHC class II + ,Ii + ,DM + tumor cells [94]. The functional role of HLA-DO molecules
in tumor antigen presentation has not yet been analyzed extensively. On the
basis of immunohistological analyses in mice, HLA-DO-mediated effects may be
limited to professional APCs. Recently, HLA-DO has been demonstrated to restrict
the MHC class II peptide binding to the late endosomal compartments, thereby influencing
the peptide repertoire presented to CD4 + T cells. Furthermore, the tumor
environment defined by locally secreted cytokines might also critically affect the coordinate
regulation of the expression of molecules required for the MHC class II
APM in a cell type-specific manner [115].
5.7.4
MHC Class II Expression in Antitumor Response
Using animal models, the role of MHC class II in the antitumor response has been
studied in syngeneic hosts. These experiments lead to the conclusion that MHC
class II surface expression on tumor cells is able to vaccinate against parental MHC
class II ± cells (Fig. 5.18). Tumor cells expressing both MHC class II molecules as
well as B7 co-stimulatory factors can stimulate a tumor-specific CD4 + T cells and result
in the eradication of pre-established invasive tumors. Co-expression of Ii with
MHC class II antigens substantially reduces the antitumor efficacy of MHC class II-
Fig. 5.18 The different MHC class II phenotypes.
There exist three distinct MHC class II
phenotypes: constitutive MHC class II surface
expression, IFN-g-inducible MHC class I surface
expression, and lack of both constitutive and
IFN-g-inducible MHC class I surface expression.