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TUMOR IMMUNOLOGY
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• Know the antigens expressed by cancer cells
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•Study how cancers evade immune system
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1
Malignant Transformation:
• The proliferation of normal cells is carefully
regulated
...
2
Tumor immunology
* Pathological cell masses derived by abnormal and
uncontrollable clonal expansion of single cell
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1) Inherited :
Expression of inherited oncogene
e
...
viral gene incorporated into host gene
2) Viral:
- Human papilloma, herpes type 2, HBV, EBV (DNA)
- Human T-cell leukemia virus (RNA)
3) Chemical:
- Poly cyclic hydrocarbons cause sarcomas
- Aromatic amines cause mammary carcinoma
- Alkyl nitroso amines cause hepatoma
4) Radiological: Ultraviolet & ionizing irradiation
5) Spontaneous: failure in the cellular growth control
4
• Cancer cells are the progeny of a single
transformed cell that undergo unregulated
cell proliferation
• A tumor may be:
Benign: If it is not capable of indefinite
growth and the host survives
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5
• This uncontrolled growth may be due to upregulation of oncogenes (cancer inducing
genes) and/or down-regulation of tumor
suppressor genes (that normally inhibit tumor
growth often by inducing cell death)
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• "Liquid" tumors are leukocyte tumors that
circulate in the blood and may also form
masses elsewhere in the body
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The following criteria serve as evidence that
tumors can elicit an immune response
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Tumors that have severe mononuclear cell
infiltration have a better prognosis than
those that lack it
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Certain tumours regress spontaneously
(e
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melanomas, neuroblastomas)
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Some tumor metastases regress after removal of
primary tumor
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Although chemotherapy leads to death of a large
number of tumor cells, the few that evade the
action of the drugs can outgrow and kill the host
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v
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8
Evidence for existence of an immune
response against tumors (ctd)
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Tumor-specific
antibodies
and
T
lymphocytes (detected in cytotoxicity and
proliferative response assays) have been
observed in patients with tumors
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The young and the old population have an
increased incidence of tumors
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viii
...
9
Tumor antigens
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• These antigens may include membrane
receptors, regulators of cell cycle and
apoptosis, or molecules involved in signal
transduction pathways
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1)
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Tumor specific antigens:
- Tumor cells develop new antigen specific to
their carcinogens
3)
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11
Tumor Associated Antigens (ctd)
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Oncofetal antigens:
a- Carcino-embryonic antigens (CEA)
- Normally expressed during fetal life on fetal gut
- Reappearance in adult life:
GIT, pancreas, biliary system and cancer breast
b- Alpha fetoprotein:
- Normally expressed in fetal life
- Reappearance in adult life; hepatoma
12
• Although chemical-, UV- or virus-induced
tumors express neo-antigens, majority of
the tumors are often weakly immunogenic
or non-immunogenic
...
13
Virus-induced tumors:
Viruses that cause tumors include
...
Papova (papilloma, polyoma) viruses
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Papilloma virus causes cervical
cancer
2
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3
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Virus-induced tumors express tumor-associated viral Ags these are cell
surface antigens that are distinct from antigens on the virion itself
...
14
Chemically-induced tumors
• Chemically-induced tumors are different from
virally-induced tumors in that they are
extremely heterogeneous in their antigenic
characteristics
...
These unique antigens on chemicallyinduced tumors are referred to as tumorspecific transplantation antigens (TSTA)
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g
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• Immunotherapy has been used as a novel
mode to treat cancer
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24
1) Active Immunotherapy: Wherein the host
actively participates in mounting an
immune response
• a)
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Bacillus Calmette-Guerin (BCG)
ii
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25
b
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Hepatitis B vaccine
ii
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Passive Immunotherapy: This involves transfer
of preformed Abs, immune cells and other factors
into the hosts
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Specific:
i
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iii
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Antibodies against tumor Ags (e
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Her2/Neu for treatment
of breast cancer)
Abs against IL-2R for Human T lymphotropic virus (HTLV1)-induced adult T cell leukemia
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Abs conjugated to toxins, radioisotopes and anti-cancer
drugs have also been used
...
E
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anti-CD20 conjugated to
Pseudomonas toxin or ricin toxin
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Nonspecific:
i
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2) Tumor-infiltrating lymphocytes (TIL)
ii
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As
tumor Ags are usually not known, tumor
lysates are used
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Cytokines
1) IL-2: Activates T cells/NK cells used in the
treatment of renal cell carcinoma and
melanoma
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2) Interferon alpha (IFN-α): Induces MHC
expression on tumors and used in the
treatment of hairy B cell leukemias
3) Interferon
gamma:
Increases
MHC
expression; for treatment of ovarian
cancers
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iv
...
29