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Chapter 20
Tumor Immunology
Contents
Introduction
PartⅠ Tumor antigens
PartⅡ Immune response to tumors
Part Ⅲ Mechanism of tumor escape
from immune surveillance
PartⅣ Immunotherapy of tumors
Introduction
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Tumor immunology is mainly to study the
immunogenicity of tumor and the mechanism of
immune response to tumor, to demonstrate the
relationship between the status of immune system and
the generation, development of tumor, to explore the
method of tumor diagnosis, therapy and prevention.
Immunosurveillance
Tumor rejection antigens are
specific to individual tumors
PartⅠ Tumor antigens

Tumor antigens: Refer to all newly
expressed antigens or over expressed
antigens during the generation and
development of the tumor.
Ⅰ.Classification of tumor antigens
Base on their patterns of expression:
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Tumor specific antigen (TSA)
Tumor associated antigens (TAA)
1.Tumor-specific antigens (TSA)
TSA: Antigens that are only expressed on tumor
cells but not on normal cells. high specificity.
Tumor high-specific antigens
TSA---only expressed on one kind of tumor,
induced by physiochemical factors, such as X-ray
Tumor low-specific antigens
TSA---expressed on more than one kind of tumor,
induced by virus
Discovery of tumor specific
transplantation antigens, TSTA
methyl-cholanthrene,MCA
Conclusion from this experiment

Tumors express antigens that are recognized
as foreign by the immune system of the
tumor-bearing host.

Immune response frequently fail to prevent
the growth of tumors.

The immune system can be activated by
external stimulator to effectively kill tumor
cells and eradicate tumors.
2.Tumor-associated antigens,TAA

Antigens that are also expressed on normal
cells, but high expressed on tumor cells.
Without tumor specificity: CEA, AFP
Ⅱ.Common human tumor antigens
1.
2.
3.
4.
Embryonic antigens
Tumor antigens induced by viruses
proteins coded by Mutated oncogene or
suppressor oncogene
TATAS expressed on human melanoma
cells
1. embryonic antigens
embryonic antigens are proteins that are express
at high levels on cancer cells and in normal
developing fetal, but peter out or very low level
in adult.
 Their main function is that they provide
markers that aid diagnosis of tumor.
Carcinoembryonic antigen (CEA)
alpha-fetoprotein (AFP)
(1) Carcinoembryonic antigen (CEA)
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High CEA level is normally restricted to cells of the
gut, pancreas, and liver in the course of 2-6 months
of gestation, and low level is found in serum of
normal adult(<5g/ml).
CEA level of serum is increased in many
carcinomas ,such as the colon, pancreas, stomach,
and breast.
The level of serum CEA is used to monitor the
persistence or recurrence of the tumors after
treatment.

CEA levels in normal individuals are below 2.5
ng/ml, but it increases significantly in certain
malignancies, particularly colo-rectal cancers.
It may also rise in some nonmalignant
conditions (e.g., chronic cirrhosis, pulmonary
emphysema, heavy smoking). Levels 4-5-fold of
normal have been used to predict recurrence of
colo-rectal tumors.
Carcinoembryonic antigen:
clinical use

Adjunct in diagnosis

Staging and prognosis

Monitoring response to therapy

Detection of tumor recurrence
Carcinoembryonic antigen:
clinical use
(2) alpha-fetoprotein (AFP)
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AFP is a circulating glycoprotein normally
synthesized and secreted by the yolk sac and liver
of fetal.
Serum levels of AFP is very low in serum of adult
(≤20ng/ml), and the concentration of AFP is up to
500ng/ml in serum of patients with
hepatocellular carcinoma.
higher rise in this protein is used for monitoring
hepatomas and testicular cancers. AFP level may
also be raised in some nonmalignant conditions,
such as cirrhosis, hepatitis and other forms of
liver damage.
Alpha fetoprotein: concentrations
Normal concentration: <20 ng/ml
 Abnormal concentrations
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100-350 possible hepatoma
350-500 probable hepatoma
500-100 likely hepatoma
>1000 HEPATOMA
2. Tumor antigens induced by viruses:
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HBV------ liver cancer
HPV------ cervical carcinoma
EBV------ B cell lymphoma and
nasopharyngeal carcinoma
3. Products of mutated genes:

Some tumor antigens are produced by
mutated genes, such as suppressor oncogenes
p53 and pro-oncogene ras
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Some patients with cancer have circulating
CD4+ and CD8+T cells that can respond to
the products of mutated genes such as Ras
and P53.
Furthermore, in animals, immunization with
mutated Ras or P53 proteins induces CTLs
and rejection responses against tumors
expressing these mutants.
Overexpressed cellular proteins and
abnormally expressed proteins:
 gp100, MAGE in melanomas
 Cancer-testis antigens
PartⅡ
Mechanism of Immune Response
T cells: αβT, γδT
NK cells

Cellular immunity
Macrophages
Dendritic cells

Humoral immunity
Ⅰ.Cell-mediated Immune Response
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T cells
NK cells
Macrophages(MΦ)
Dendritic cells (DCs)
1. T lymphocytes:
(1) T cells
The principal mechanism of tumor immunity is killing of
tumor cells by CTL
Tumor antigens
DC cross presentation
CD4+Th cells
CD8+T（CTL）
(2) T cells
Non-classⅠMHC restriction
Its target cells are not hypersensitive to NK
cells
First line of defence of immune surveillance
2. NK cells:
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NK cells are broad-spectrum killer cells
It can kill target cells with low level or non
MHC class Ⅰmolecule.
First line of defence of immune surveillance
activated
Tumor cell
3. Macrophages(MΦ)
① APC
② release of lysosomal enzymes, reactive
oxygen intermediates, nitric oxide
③ ADCC
④ secrete cytokines
4. Dendritic cells:
① APC------Induce adaptive immune response
② Inhibit tumor growth directly
IR-Mediated Tumour Elimination
NKT
γδT
NK
NKT
NK
NKT
NK
γδ T
CTL
NK
CD4
CTL
CTL
NK
CTL
CXC10-12
IFNγ
DC
Innate IR
recognises
tumour cell
establishment
CD4
IFNγ
DC
LN
NK cells and other
effectors recruited to
site by chemokines,
which also target
tumour growth directly.
IFNγ
CXC10-12
MΦ
MΦ
MΦ
Tumour-specific T cells
home to tumour site, along
with macrophages and
other effectors to eliminate
tumour cells.
Ⅱ. Humoral immune responses
Antibodies:
① Activating complement
② ADCC
③ Opsonization
Antitumor Effector Mechanisms
CTL
NK cell
Tumor cell
Humoral
Mechanisms
Macrophage
Kumar et al. Basic Pathology 6th ed. Figure 6-32
PartⅢ Mechanism of Tumor
Immune Escape
Factors related to tumor cells
Factors related to the host’s
immune system
Ⅰ. Factors related to tumor cells
1.low immunogenicity of tumor antigens
and antigenic modulation
(1) low immunogenicity of tumor antigens
The failure of immunosurveillance may be the
fact that in the early development of a tumor, the
amount of antigen may be too small to stimulate
the immune system.
Escape from immunosurveillance
Lack of
Neo-antigens
(2) antigenic modulation: is a phenomenon that
cell-surface tumor antigens are decrease or lose
because of attack of host’s humoral immune.
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2. covering or blocking of tumor antigens on
the surface of the tumor cells
3. Diminution or absence of MHC class I
molecule
4. Lack of co-stimulatory molecule on the
surface of tumor cells
5. Immune inhibitors secreted by tumor cells
Escape from immunosurveillance
Ⅱ.Factors related to host’s
immune system

1. Immunodeficiency

2. Suppressing immune function by tumor
directly or indirectly
PartⅤ Immunotherapy of tumors
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Active immunotherapy
Target immunotherapy
Adoptive immunotherapy
Cytokine therapy
Gene therapy
Stimulation of active host immune
responses to tumors:
 Vaccination with tumor cells and tumor
antigens, or with APC.
 Augmentation of host immunity to tumors
with cytokines and costimulators
 Nonspecific stimulation of the immune
system
Vaccination
with tumor cells and tumor antigens
DC:
Use “primed” dendritic cells
 APCs can be fed tumor antigens in the laboratory
and then injected into a patient. The injected cells are
primed to activate T cells
 Alternatively, DCs can be infected with a viral vector
that contains the gene for a tumor antigen.
Use of tumor specific/associated
antigens monoclonal antibodies

Adoptive immunotherapy
Adoptive cellular immunotherapy is the transfer of
cultured immune cells that have anti-tumor
reactivity into a tumor-bearing host.
LAK, TIL, CD3AK, CTL
Passive immunotherapy for tumors with
T cells and antibodies:
 Therapy with anti-tumor antibodies:
Monoclonal antibodies conjugated drugs
 Adoptive cellular therapy:
LAK,TIL,CD3AK,CTL
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Cytokines may also be administered
systemically for the treatment of human
tumors.
IL-2 works by stimulating the proliferation
and anti-tumor activity of NK cells and
CTLs.
IFN-γworks by increasing the cytolytic
activity of NK cells and class I MHC
expression on various cell types.
Their side effects limited this treatment.
Augmentation of host immunity to tumors
with cytokines and costimulators