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combined with EBRT on lung metastasis from esophageal
cancer. The representative optical images show lung
metastatic burden detected by D-luciferin assay.
Figure 2.
The therapeutic efficacy of
188
Re-liposome
combined with EBRT on lung metastasis from esophageal
cancer. Low-dose whole lung EBRT with 3 consecutive
daily fractions of 1 Gy was delivered followed by
intravenous
188
Re-liposome (250 µCi) administration in
combination group. N=3 for each group.
Conclusion
The combination of low-dose whole lung EBRT with
systemic
188
Re-liposome administration might be a
potential treatment modality for lung metastasis from
esophageal
cancer.
Modulation
of
tumor
microenvironment by the combination treatment is
warranted in translational research. This proof-of-concept
study needs to be validated by clinical investigation.
PO-0993 Influence of radiotherapy on differentiation,
maturation and functionality of dendritic cells
L. König
1
, A. Gardyan
2
, J. Hörner-Rieber
1
, P. Huber
2
, K.
Herfarth
1
, S. Rieken
1
1
University Hospital Heidelberg, Department of
Radiation Oncology, Heidelberg, Germany
2
German Cancer Research Center- Heidelberg, Clinical
Cooperation Unit Molecular Radiooncology-, Heidelberg,
Germany
Purpose or Objective
Primary purpose of radiotherapy (RT) is elimination of
cancer cells by inducing DNA-damage that either causes
induction of tumor cell death or inhibition of the
proliferating capacity of these cells. In addition,
considerable evidence emerges that antineoplastic effects
extend beyond these mechanisms. These secondary
effects can contribute to anti-tumor responses in a local
but also systemic manner via activation of the immune
system: The role of dendritic cells (DCs) is well described
to be essential for priming effective radiation-induced
adaptive immunity. Through increased release of tumor-
associated antigens (TAA) after RT, DCs are recruited and
cross-presentation of TAA leads to activation of B- and T-
lymphocytes, therefore playing a pivotal role in adaptive
immune response and immunogenic cell death. However,
there are still many hypotheses regarding the influence of
RT on activation of the immune system. The aim of our
experiments is to further characterize the impact of
different radiation types and dosages on differentiation
and functionality of DCs.
Material and Methods
Human CD14-positive monocytes were isolated from
peripheral blood mononuclear cell samples of six
individuals. In the presence of appropriate cytokine
stimulation with Interleukin-4 (IL-4) and granulocyte
macrophage
colony-stimulating
factor
(GM-CSF)
monocytes were induced into immature DCs (iDCs) and
later mature DCs (mDCs). Monocytes were irradiated with
different photon radiation doses (1x15Gy, 5x2Gy,
1x0.5Gy) on day 0. Maturation to mDCs was induced on day
7 by adding tumor necrosis factor alpha (TNFα) to the
culture medium. Differentiation and maturation of DCs
was assessed on day 2, 9 and 12 by staining of the cell
surface molecules CD14, CD83, CD80, CD86 and HLA-DR via
flow cytometry. Functional analysis of irradiated DCs was
performed through FITC-labelled phagocytosis assay.
Results
No major significant changes in the immune profile during
differentiation of monocytes (CD14
high
, CD83
low
, CD86
low
,
CD80l
ow
, HLA-DR
high
) into iDCs (CD83
low
, CD86
low
,
CD80
medium
, HLA-DR
medium
) and mDCs (CD83
high
, CD86
high
,
CD80
high
, HLA-DR
high
) were seen after treatment with
different radiation doses (1x15 Gy, 5x2 Gy, 1x0.5 Gy)
compared to the untreated control group. Functional
analysis showed no difference in the phagocytotic capacity
of irradiated iDCs and macs compared to the control
group.
Conclusion
Our experiments reveal that after irradiation with
different fractionations and doses maturation of DCs was
unchanged compared to the control group. The capability
for phagocytosis was unaffected after irradiation of DCs,
indicating persistent functionality of the immune system.
Additional RT-induced effects on the immunogenic
potential of DCs will be investigated by using further
functional assays (migration assay, mixed lymphocyte
reaction assay). To investigate the effect of particle
therapy, DCs will be irradiated with protons and carbon
ions (C12) in future experiments.
PO-0994 Integrin antagonistic drugs reveal different
effectiveness in 2D monolayer vs. 3D spheroid culture
V. Kopatz
1,2
, E. Selzer
1
, W. Dörr
1,2
1
Medical University of Vienna, Department for Radiation
Oncology, Vienna, Austria
2
Medical University of Vienna, Christian Doppler Lab for
Medical Radiation Research for Radiooncology, Vienna,
Austria
Purpose or Objective
Preclinical evaluation of novel therapeutic substances, as
well as the assessment of radiation effects, is frequently
performed under standard 2D cell culture conditions.
However, such monolayer cultures may fail with regard to
representation of morphological in vivo conditions and
their (radio)biological consequences. An alternative, in
the latter aspect is the use of 3D in vitro models - like
tumor spheroid culture - which are of intermediate
complexity between standard in vitro monolayer cultures
and in vivo tumor models. In spheroid culture, tumor cells
grow in 3D aggregates that display greater similarity to in
vivo tumor architecture and growth conditions, such as the
presence of oxygen and nutrient gradients as well as more
complex cellular interactions or 'in vivo-like” gene
expression profiles. Depending on their size, multicellular
spheroids may also display central hypoxic and/or necrotic
areas and show quiescent and proliferating
compartments. Thus spheroids often depict different
behavior and sensitivity towards certain drugs or
radiotherapeutic treatment as cells cultured as 2D
monolayers. Especially for the study of surface receptors
like integrins the 3D structure and environment is a critical
aspect as these receptors transduce signals from the
extracellular space to the inside, thus influencing
different cell signaling pathways like cell survival,
proliferation and invasion.
Material and Methods
Therefore in addition two standard 2D cell culture, 3D
spheroid models were established with 518A2 and other
melanoma cell lines for evaluation of their response to two
different integrin antagonists, cilengitide and a novel
integrin antagonist (NIA), as well as for the
characterization of the effects of radiation treatment
alone or in combination with the drugs.