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Lee Cell-mediated immunotherapy for HCC

patients with advanced stage HCC, so the search for
effective treatments is a crucial one.

Cancer cells occur as a consequence of enhanced or
aberrant expression of oncogenes or from loss of tumor
suppressor genes. Cancer cells with genetic change
will express new antigens [13] . These tumor-specific or
tumor-associated antigens might be recognized by
antigen-presenting cells and trigger T-lymphocytes to
conduct anti-cancer immunity [14-16] . Immunotherapy
has been studied as an attractive and novel therapeutic
strategy to treat cancer since a few decades ago. This
brief review will focus on cell-mediated immunotherapy
for HCC.
Figure 1: Dendritic cells can be pulsed by tumor DNA, RNA and
proteins to activate antigen-specific T-cells. These activated T-cells
IMMUNITY IN CANCER can produce antigen-specific cytotoxicity to eradicate tumor cells

The immune system is the most important protection
for a host in defending itself from foreign invaders and activated T-cells is directly related to efficacy of
cancer development. As noted, cancer cells occur as cancer treatment. In animal studies, tumor-infiltrating
a consequence of enhanced or aberrant expression lymphocytes in tumor-bearing hosts have been proved
of oncogenes or loss of tumor suppressor genes. The anergic to cancer cells. Cancer cells may also induce
cancer cells with genetic change express new antigens T-cell apoptosis or regulatory T-cells, which conduct
[26,27]
and the new antigens may be captured and processed peripheral tolerance to cancer cells . Clinically,
by dendritic cells (DCs) to trigger T cell-mediated we have already observed that the percentage of
immunity [17,18] . lymphocytes decreases along with tumor growth in
HCC patients [25] . In patients with significant numerous
Dendritic cells, the most potent and professional tumor mass, the percentage of lymphocytes is always
antigen-presenting cells, constitutively express major below normal range. Immediately before patients
histocompatibility complex (MHC) class I and II and die of HCC, lymphocytes cannot even be detected.
high levels of costimulatory molecules CD40, CD80, Obviously, lymphocytes are suppressed by HCC
and CD86. When DCs meet antigens, they capture through currently unidentified mechanisms.
antigen, process it, and present the antigen to activate
antigen-specific cytotoxic T-cells. Clinically, DC- Regulatory T cells are immune suppressive cells [28] . In
based immunotherapy has been applied to treat end- animal models, depletion of regulatory T cells causes
stage patients with B-cell lymphoma [19] , melanoma [20] , inflammatory colitis, and restoration of regulatory T
renal cell carcinoma [21] , prostate cancer [22] and other cells can prevent inflammatory colitis [29] . Therefore,
+
+
tumors [23] . The results are promising [24] . DC-based natural regulatory T cells, CD4 CD25 CD45RBlow, are
immunotherapy offers a hope of successful eradication considered important cells in maintaining peripheral
of cancer [Figure 1]. tolerance. Regulatory T cells are also recognized as
playing an important role in cancer diseases [30] . For
However, DC-based immunotherapy yields only a 20% gastric [31,32] , esophageal [33] , and other gastrointestinal
response rate in most of the clinical trials for advanced malignancies, regulatory T cells were increased in
cancer diseases [25] . These results suggest that, even peripheral blood. For breast cancer, regulatory T cells
though DCs are the most powerful antigen-presenting were increased in peripheral blood and in the tumor
cells, the immune system of most advanced cancer microenvironment [34] . For lung cancer, regulatory T
patients cannot be activated or may only be activated cells selectively inhibited host immune response and
to a limited extent by DC. It is hoped that exploration may have contributed to disease progression [35] . For
of immunosuppressive mechanisms in tumor-bearing HCC, CD4 CD25 regulatory cells are also found
+
+
patients will improve the success of DC-based or cell- in the tumor by immunohistochemical staining, and
mediated immunotherapy. the number of regulatory T cells is correlated to the
prognosis. In our previous study, regulatory T-cells
IMMUNODEFICIENCY IN CANCER PATIENTS were identified in the tumor microenvironment. The
number of regulatory T-cells was correlated to tumor
T-cells are the direct effector cells that attack and size and contributed to prognosis. These regulatory
eradicate cancer cells. The cytotoxic ability of T cells also appeared to suppress the DC-mediated
Journal of Cancer Metastasis and Treatment ¦ Volume 3 ¦ October 31, 2017 245