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

78 5 Major Histocompatibility Complex Modulation and Loss
Fig. 5.16 HLA-C locus expression. This particular
altered MHC class I phenotype expresses
only HLA-C locus products. It is hypothesized
that these tumor cells could escape from both T
cell and NK cell-mediated cytotoxicity.
ity of colorectal (2.5%), laryngeal (5%) and breast carcinoma (9.5%) cells, respectively,
thereby escaping not only from the CTL, but also from NK cell-mediated recognition
[87].
To overcome the potential hurdle of allele-specific loss during immunotherapy, the
induction of multispecific responses using a combination of peptides derived from
TAAs will help to solve this problem. This strategy may counteract the ability of tumor
cells with selective MHC class Iallele loss to escape from immune recognition
[88]. The biological significance of decreased MHC class Isurface expression as a
possible tumor escape mechanism from immune recognition is presently unclear,
but is based on four different experimental approaches and observations: (1) CD8 +
cytotoxic T cells can recognize one MHC/peptide complex which is sufficient to lead
to CTL-mediated tumor lysis; (2) the expression of MHC class Ican often be upregulated
by IFN-g which is commonly secreted by effector CTLs; (3) decreased levels
of MHC class Iexpression render tumor cells more susceptible to NK cellmediated
lysis and (iv) the MHC class I-negative phenotype can be associated with
poor survival [89]. However, a global down-regulation of MHC class Iand TAP1 does
not account for the ability of all tumors to evade the immune system. For example,
impaired MHC class Iantigen and TAP1 expression rarely occurs in NK/T cell lymphoma,
suggesting that other immune escape mechanisms such as the production
of IL-10 appear to suppress the local immune response [90].
There exist a number of studies demonstrating that IFN-g induces MHC class Isurface
expression in a variety of human tumors of distinct histology which is at least
partially due to an up-regulation of different components of the MHC class IAPM.
These data suggest that adjuvant IFN-g immunotherapy may be of benefit for patients
in the case of MHC class I ± tumors. Local inflammation and immunization
processes may induce or amplify the IFN-g production of effector cells which could