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

182 9 Dendritic Cells and Cancer: Prospects for Cancer Vaccination
phoid tissue. They produce interferon (IFN)-a in these locations and are thought to
contribute to the innate immune response [6]. Recent data suggesting that they can
be recruited to inflammatory sites [57] and can present antigen for primary
T lymphocyte responses (Vuckovic et al., in preparation) suggests an even more complex
set of cellular interactions than formally thought is possible within responding
secondary lymphoid tissues.
Preliminary evidence also exists for the ability of DCs to interact directly with NK
cells and activate them [58]. DCs and NK cells might interact at a peripheral site
(e.g. tumor site), where they can be recruited through chemokines. Their activity
may result in tumor lysis, releasing apoptotic or necrotic bodies that will be taken
up, transported and presented by DCs to T lymphocytes. Cross-talk between DCs
and NK cells may serve as another mechanism through which DCs can elicit and enhance
an effector immune responses, and link the innate and adaptive immune responses.
9.3
DC in Human Cancer
If the DCs are to mount a protective response to an early cancer, the DCs must sense
ªdangerº, react appropriately and present relevant TAAs to the immune system. This
has now been studied in several human cancers. Immunohistological analysis of renal
cell carcinoma suggested that DCs were present in normal numbers in the malignant
tissue and no evidence of increased activation was found [59]. Similar findings
were made in prostate cancer [60], and by us [61] and others [62] in breast cancer.
Bladder cancers likewise had normal numbers of DC1 a ± DCs present, consistent
with their superficial epithelial location [63]. It proved possible to isolate the DCs
from renal cell carcinoma and basal cell carcinoma [64], and these cells appeared to
have low stimulatory capacity. Notably, the DCs present in draining lymph nodes
likewise had apparently reduced allostimulatory capacity [65].
These findings may be integrated with a more extensive body of literature using
S100 staining to identify DC in human tumors, notably head and neck as well as gastrointestinal
tumors [66, 67]. In these studies, a correlation between S100 staining
and positive prognosis has been a common finding. A correlation between S100
staining and the subset of activated DCs identified by the CMRF-44 mAb [68] suggests
that a good prognosis relates to the number of DC which are activated in the tumor
environment ± exactly as predicted.
Reduced blood DC counts in cancer patients have been described [69]; however, this
finding may vary with the stage of disease as our studies suggest (Ho et al., in preparation).
DC counts are preserved in patients with stage Iand IIbreast cancer. Likewise,
blood DC counts in patients with multiple myeloma appear to be relatively preserved
but systemic defects in the ability of the DC to up-regulate co-stimulator molecules
were noted [70]. A subset of Lin ± HLA-DR ± cells present in the blood of cancer
patients identified as immature myeloid cells has also been suggested to inhibit
blood DC function [71].