immunity to tumor

Dr. Ahmed Adil Immunology 3rd class-college of Medicine
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Immunity to Tumor
Tumor cells:-
Are cells that no longer respond to the usual checks and balances for division and
death. Human carrying a chemical (free radicals) or viral genes (Oncogenes) which
can induced malignant tumor. Cancer may also induced by a mutation in cellular
genes like tumor suppressor genes& those regulate apoptosis(programmed cell
death) .
Development from a normal cell to a cancerous one requires transformation steps
(initiation and promotion).
Tumor associated antigens:
Transformed tumor cells express characteristic cell surface antigens and these
antigens often initiate immune responses.
In the course of neoplastic transformation, new antigens, called tumor-associated
antigens(TAA), develop at the cell surface and the host recognizes such cells as
"nonself" and an immune response to that tumor may induced and cause its
regression .Some tumor cells can escape immune response (surveillance) by
"modulation," i.e., internalizing or losing the surface antigen particularly MHC I &
II , so that they are no longer present as a target for immune attack.
Some of most common TAA are:
1- TSTAs (Tumor Specific Transplantation Antigen).
? Unique to tumor cells&do not occur on normal cells in the body.
? Novel proteins created by mutation affect class I MHC genes either
chemically, physically or virally induced.
Dr. Ahmed Adil Immunology 3rd class-college of Medicine
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2- TATAs(Tumor Associated Transplantation Antigen)
Not unique to tumor cells and do occur on normal cells in the body
So where’s the problem?
? Fetal /adult presence(Oncofetal Ag.)
? High levels of growth factors and growth factor receptors. [Breast
cancer cells have high level of the growth factor receptors “ Neu”
which found in small amount on normal cells].
3- Viral Antigen
a- Viral proteins and glycoproteins .
b- New antigens produced by virally infected host cells under control of viral
nucleic acid.
4- Oncofetal antigens
a- Alpha fetoprotein
b- Carcino-Embryonic Antigens (CEA)
Both Normally expressed during fetal life before immunocompetence and If
reappearance later in adult life it indicate a
Dr. Ahmed Adil Immunology 3rd class-college of Medicine
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Mechanisms of tumor immunity
During neoplastic transformation, new antigens develop and the host recognize
them as non self-antigens.Cell mediated immune is the main response which
attacks these non self -tumor cells. Immune response acts as surveillance system to
detect and eliminate newly arising neoplastic cells.
Immune Surveillance theory suggests that:
1-cancer cells frequently arise within the body but are normally eliminated before
they multiply sufficiently to become clinically detectable.
2-Tumors arise only if they are able to escape immune surveillance
The immune response include :
1- Natural killer (NK) cells
They specialize in killing virus-infected cells and tumor cells by secreting
cytotoxins (perforins and granzymes) similar to those of cytotoxic T lymphocytes
and by participating in Fas-Fas ligand-mediated apoptosis. Killing is MHC
independent and helped by interferon ? and IL-12. They can kill without antibody,
but antibody (IgG) enhances their effectiveness, a process called antibodydependent
cellular cytotoxicity (ADCC).NK cells detect the presence of cancer
cells by recognizing a protein called MICA that is found on the surface of many
cancer cells but not normal cells. Interaction of MICA with a receptor on
NK(KAR) cells triggers the production of cytotoxins by the NK cell and death of
the tumor cell.
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Dr. Ahmed Adil Immunology 3rd class-college of Medicine
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e- Macrophage activation factor.
4-B-cells(Antibody) :
Tumor associated antigens stimulate production of specific antibodies by host
plasma cells. These specific antibodies bind together on tumor cell surface leading
to destruction of tumor through:
a- Antibody-dependent cellular cytotoxicity (ADCC) killing by NK and M?
b- Activation of classical pathway of complement.
Some antibodies called blocking antibodies may enhance tumor growth, perhaps
by blocking recognition of tumor antigens by the host cell mediated immunity.
Tumor markers
Some human tumors contain antigens that normally occur in fetal but not
in adult human cells, the most common are:
1. Carcinoembryonic antigen (CEA)
Circulates at elevated levels in the serum of many patients with
carcinoma of the colon, pancreas, breast, or liver. It is found in fetal gut,
liver, and pancreas and in very small amounts in normal sera.
This antigen can be detected by radioimmunoassay,If the level declines after
surgery, it suggests that the tumor is not spreading.Conversely, a rise in the level
of (CEA) in patients with resected carcinoma of the colon suggests recurrence or
spread of the tumor.
2-Alpha fetoprotein is present at elevated levels in the sera of hepatoma patients
and is used as a marker for this disease. It is produced by fetal liver and is found in
small amounts in some normal sera.