الفهرس 
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Abstract
Hepatocellular carcinoma (HCC) is the third most frequent cause
of death from cancer worldwide, which accounts for about 6% of all
newly diagnosed cancer cases worldwide (Tagliamonte et al., 2016).
Current therapies for early disease, which include liver transplantation,
surgical resection or local ablation, do not lead to long-term cure in the
majority of patients with advanced HCC (Chaparro et al., 2008).
The immune evasion in HCC represents a main barrier to the
delivery of an effective immunotherapy (Raufi and Tirona, 2017).
Therefore, inhibiting the immune suppressive effect of cancer cells
represents an important step in cancer immunotherapy. Although
protocols differ, a common outline in immunotherapy is the activation
of dendritic cells (DCs) in order to enhance antigen presentation.
Studying the surface and molecular markers can aid in evaluating
efficient immunotherapeutic tools (Wang et al., 2015).
The present study aimed to enhance antigen presentation of
tumor-associated antigens (TAAs) by attenuating liver cancer cells
using ribonuclease A and subsequent co-culturing cancer cells with
their autogenic or allogenic DCs and lymphocytes.HCC patients were fully diagnosed by means of clinical,
radiological and laboratory examinations before being selected in the
present work. Successful culturing of HCC core biopsy was
approximately 15 out of 50 specimens which was therefore selected in
the current study.
Blood samples and liver core biopsy were obtained from fifteen
newly diagnosed HCC patients. Peripheral blood mononuclear cells
(PBMCs) were isolated and lymphocytes and monocytes were further
isolated from the isolated PBMCs using tissue culture. Monocytes were
then propagated and differentiated to immature dendritic cells. HCC
explants were cultured in vitro to liberate cultured cancer cells. Cancer
cells (HepG2 or patient’s HCC cells) were attenuated by
ribonuclease A, meanwhile only HCC cells were treated with sorafenib
and a group of untreated cells act as a control. Gene expressions of
CD44, TAP-2, LMP-2, lactate dehydrogenase (LDH) and
interleukin-12 levels in culture media supernatant and
immunophenotypes of the cultured immune cells were evaluated.
The results are summarized as follows:
• Attenuating HepG2 cells with ribonuclease A and subsequent
pulsation to allogenic immune cells showed a paradoxical effect on
antigen presentation.
• Attenuating HCC cells using ribonuclease A and subsequent pulsation
to its autologous immune cells showed enhanced presentation of
tumor associated antigens.• Treating HCC cells with sorafenib and subsequent pulsation to its
autologous immune cells did not show significant change in antigen
presentation.
• Combination of ribonuclease A attenuation and sorafenib treatment of
HCC cells showed the lowest antigen presentation confirming their
antagonism.