Lecture 13

Tumor
Immunology
Saleh Bahaj
Prof. of Medical
Microbiology/Immunology
 Objectives
By the end of this lecture the students should be
able to:-
I) Immune surveillance & Tumor Ag
II)Immune response against tumor
III) Tumor evasion
IV) Tumor Markers
V) Tumor Immunotherapy
VI) Test yourself
 I) Immune
surveillance
 I) Immune surveillance

 Million cells/day

Oncogenic changes
 I) Immune surveillance

Immune surveillance is
daily continuous
screening of all body cells
by immune system to
recognize and destroy
tumor cells
 I) Immune surveillance

The cells involved in

immune surveillance
are
* NK cells
* Macrophages
* Cytotoxic T cells
 I) Immune surveillance
means Normal
cell
a foreign Ag on
tumor cells
MHC I
(Tumor Ag)
Tumor
cell
Tumor Immunology
Evidence of immune
response against tumor
Evidence of immune response against tumor

1
Immunosuppressed
patients
 ADIS Kaposi sarcoma
Evidence of immune response against tumor

2
Extremes age
 Very young Frequency
 Very old of tumor
Evidence of immune response against tumor

3
Antibodies & T
lymphocytes detected in
tumors
Evidence of immune response against tumor

4 HBV vaccine
Immunization against
some tumor
Hepatocellular
carcinoma
Tumor antigens
 I) Tumor antigens
Cell surface molecules that appears on
tumor cell & Recognize by Immune system

MHC I

Normal Tumor
cell cell
I) Tumor antigens
 I) Tumor Antigen

1) Tumor specific
antigens
2) Tumor associated
antigens
 Tumor antigens
1) Tumor specific antigens
 1) Tumor specific antigens

 Present only Tumor

in tumor cells cell
(Exclusive)
1) Tumor specific antigens
A) Viral transformation

 Virus
Cell
 HBV
 HPV Viral Ag
 1) Tumor specific antigens
B) Genetic mutation

 Carcinogen
 X-ray Normal Tumor
 Mutant P53 cell cell

Not present in normal Tumor Ag

cell
 Tumor antigens
1) Tumor specific Ag

2) Tumor Associated Ag
 2) Tumor Associated Ag

These antigens MHCI

Normal
present in normal cell
cells
But Increased in
Tumor
tumor cell
(Not unique to tumor cells)
 2) Tumor Associated Ag

1) Oncofetal antigens
 AFP
 CEA
 2) Tumor Associated Ag

2) HER2 is found on
normal cells in very low
amounts
HER2
Overexpression on
breast cancer
 2) Tumor Associated Ag

Prostatic specific Ag
present in trace amount

Increased in
Prostatic cancer
Tumor Immunology

II) Immune response

against tumor
 Exercise 2
How can the immune system
eliminate the below tumor cell?

Tumor
cell
 Answer of Exercise 2
IL-2, INFγ, TNF TH1 TH2 BCGF & BCDF
cell cell 5
Opsonization
1 IL-2
B cell

2 INFγ
Tumor
TNF cell
3 TNF 6 ADCC

4 Complement
IL-2 LAK 7 Activation
 III) Tumor evasion
(Escaping from immune response)
 Exercise-3

Why there is
no immune response?
 III) Tumor evasion
(Escaping from immune response)
1) Immunosuppression
 1) Immunosuppression

A) Host B) Tumor
 1) Immunosuppression
By Host
Immunosuppressed
patients
 Transplant
 ADIS
 1) Immunosuppression
By Tumor Transforming growth factor
(TGF-β)

Tumor
Inhibit proliferation &
cell function of lymphocytes
& macrophages
 1) Immunosuppression
By Tumor CD4 CD25

CTLA-4

Foxp3
Tumor Treg
cell
Inhibit T cell response
to tumor Ag
 1) Immunosuppression

By Tumor
Fas Fas L
Tumor Tc
cell

Tumor cells express Fas Ligand

Fas L Fas
Tumor
cell Tc
 III) Tumor evasion
(Escaping from immune response)

2) Tumor Ag
 2) Tumor Ag
a) Too small to be detected Ag
(Sneaking through)

Tumor
cell
Tumor No response
cell
Weak antigens
 2) Tumor Ag

b) Lack Ag Tumor
cell
No Ag
 2) Tumor Ag
c) Fibrin coat around tumor

Tumor
cell
 2) Tumor Ag
d- Antigenic shedding by tumor
cells

Tumor
cell
 2) Tumor Ag
e) Blocking antibodies

Tumor
cell

Non-complement fixing anti-tumor

antibodies
 III) Tumor evasion
(Escaping from immune response)

3) Reduction of MHC I
 3) Reduction of MHC I
MHC I Tc
Cell Tumor
cell
(CTL resistant but NK Tumor cells become
sensitive) resistant to cytotoxic T
cells
 III) Tumor evasion
(Escaping from immune response)

4- Lack of co-stimulation
4- Lack of co-stimulation

APC
CD28
B7
4- Lack of co-stimulation

APC MHCI TCR

(Tumor
cell) B7 CD28
Tc
IV) Tumor Markers
 Exercise 4
Predict what are the Characters of
Ideal Tumor Marker?
 Answer of Exercise 4

1
Present on
Tumor
cell

tumor cells not

normal cells Normal
cell
 Answer of Exercise 4

2
Specific for
tumor type

AFP
 Answer of Exercise 4

3
Present in all
patients with
this tumor
AFP
 Answer of Exercise 4

4
Early
Detected
AFP
 Answer of Exercise 4

5
Present in
Tumor mass
Marker
concentrations Tumor mass
proportional to
Marker
tumor mas
IV) Tumor Markers
 IV) Tumor Markers

1
Alpha fetoprotein
(AFP)
Hepatoma
NR 0-20 ng/ml
 IV) Tumor Markers

2
Carcinoembryonic
antigen (CEA)

NR below 2.5 ng/ml

 IV) Tumor Markers

3
β-subunit of
Choriocarcinoma

human chorionic
gonadotrophin
(β-HCG)
 IV) Tumor Markers

4
Prostatic specific
antigen(PSA)
Prostatic acid
phosphatase (PAP) Prostatic
tumor
IV) Tumor Markers

5
CA 125
 IV) Tumor Markers

6
CA 19-9
 IV) Tumor Markers

7
CA 15-3

Breast cancer
 V) Tumor
Immunotherapy
 V) Tumor Immunotherapy
 Specific  Non-Specific

A)passive B) Active
1) Humoral
2) Cellular
1)Tumor vaccine
3) Combined
 Non-specific Immunotherapy

Cell
 BCG
mediated
vaccine Immunity
(At the site of
tumor)
 V) Tumor Immunotherapy
 Specific  Non-Specific

A)passive B) Active
1) Humoral
2) Cellular
1)Tumor vaccine
3) Combined
 V) Tumor
Immunotherapy
A) Passive
Immunotherapy
1) Humoral
1)Humoral (Monoclonal Antibodies)

Magic bullet
therapy
1)Humoral (Monoclonal Antibodies)
Magic bullet therapy
ADCC & Complement
activation
Cancer
cell
Cancer cell
Aby linked with
cytotoxic drug

Toxin, Radioactive,
Cytotoxic drug
1)Humoral (Monoclonal Antibodies)
Y
Linked with radioactive
Anti-CD20
CD20
 Anti-CD20
 For treatment of B cell
B cell lymphoma
Rituximab
1)Humoral (Monoclonal Antibodies)

 Anti-HER2

Herceptin
Trastuzumab
 V) Tumor Immunotherapy
 Specific  Non-Specific

A)passive B) Active
1) Humoral
2) Cellular
1)Tumor vaccine
3) Combined
 V) Tumor
Immunotherapy
A) Passive
Immunotherapy
2) Cellular therapy
(Adoptive)
 2) Cellular therapy
a) Lymphokine - activated killer
cells (LAK)
NK cells 3 days
from patient Re-infusion into
+ the patient
IL-2 LAK cells
 2) Cellular therapy
b) Tumor-infiltrating lymphocytes (TIL)

Tumor
cell
Lymphocytes
from tumor Tc
\
Re-infused into
Surgical removal
the patient
of cancer IL-2
 2) Cellular therapy
c) Tumor-infiltrating lymphocytes (TIL)
(New approach)
Lymphocytes

+
Tumor from tumor
cell
Tumor Ag Re-infused

+
Surgical
removal of
cancer
IL-2
 V) Tumor Immunotherapy
 Specific  Non-Specific

A)passive B) Active
1) Humoral
2) Cellular
1)Tumor vaccine
3) Combined
 V) Tumor
Immunotherapy
A) Passive
Immunotherapy
3)Combined
 3) Combined therapy
Cytotoxic T
cell/NK cell
Tc

Y
Y Monoclonal
antibody

Tumor
 V) Tumor Immunotherapy
 Specific  Non-Specific

A)passive B) Active
1) Humoral
2) Cellular
1)Tumor vaccine
3) Combined
 B) Active Immunotherapy

Tumor vaccine
 1)Tumor vaccine

Irradiated Adjuvant
tumor cells
A)Tumor cell
vaccine Injected into the
patient
 1)Tumor vaccine

B)Tumor antigen Tumor

cell
vaccine
Synthetic
peptide vaccine
 1)Tumor vaccine
HPV
C) Tumor viral
vaccine
Vaccine of
HPV
 1)Tumor vaccine

HBV
 Tumor viral
vaccine

Vaccine of HBV
 V) Tumor Immunotherapy
 Specific  Non-Specific

A)passive B) Active
1) Humoral
2) Cellular
1)Tumor vaccine
3) Combined
VI) Test yourself
 Q1
Which of the following cells are effective
against a tumor?
B cells
Mast cells
T cytotoxic cells
Monocyte
NK cells
2-3 days
 Q2
Which of the following causes an increase
expression of class I MHC?
γ-INF
TGF-alpha
IL-2
Monocyte
Monocyte
2-32-3
days
days
TNF
 Q3
Lymphocytes cells from patients with
tumors are treated with IL-2 to get
Lymphokine activated killer cells (LAKs)
Tumor infiltrating lymphocytes (TILs)
Magic bullet therapy
Monocyte
Tumor antigen vaccines
2-3 days
 Q4
NK cells from patients with tumors are treated
with IL-2 to get

Lymphokine activated killer cells (LAKs)

Tumor infiltrating lymphocytes (TILs)
Magic bullet therapy
Monocyte
Tumor antigen vaccines
2-3 days
 Q5
Which of following mechanisms may
contribute to tumor evasion?
Lack of expression of MHC II on tumor cells

Lack co-stimulatory signals

Secretion of immunosuppressive by certain tumors
Monocyte
Lack of antigens
2-3 dayson tumor cells
 Q6
What is the marker for colon cancer?

Alpha fetoprotein(AFP)
CA 15-3
Carcinoembryonic antigen (CEA)
Monocyte
CA 125
2-3 days
 Q7
What is the marker of hepatoma?

Prostatic specific antigen

Bence Jones protein
Hepatitis B surface antigen (HBsAg)
Monocyte
Alpha fetoprotein(AFP)
2-3 days
 Q8
Cells of the innate immune system that have an
important role in recognition of tumor cells and
their destruction are:
B cells
Neutrophils
T cytotoxic cells
Monocyte
NK cells
2-3 days
 Q9
Lack of expression of which co-stimulatory
molecule by tumor cells results in weak T cells
activation?
CD28
B7
CD3
Monocyte
CD4
2-3 days
 Q10
What is the passive humoral immunotherapy
in treating tumor?

Monoclonal antibodies linked to toxic drugs

Injecting killed tumor cells
Use of lymphokine activated killer cells
Monocyte
Use of tumor infiltrating lymphocytes
2-3 days
Th
an
k yo
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