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Tumor Immunology

Wirsma Arif Harahap


Surgical Oncologist
Surgery Department
Andalas Medical School

Immune System
A complex of
lymphoid organs
highly specialized
cells
circulatory system
separate from
blood vessels

Immune System
Lymphatic vessels
form a circulatory
system that operates
in close partnership
with blood circulation
Carries lymph, a fluid
that contains WBCs
(chiefly lymphocytes)
Lymph nodes provide
meeting grounds

Four Primary Functions


Recognition of self
self-tolerance
immunological
privilege
Immunosurveillance
Intracellular
hormones
Defense against
infection

Role of the immune


Virus
Parasites
system is to protectTapeworms
Influenza
Polio mellitus
Malaria
from:
Helminths

Fungi

Bacteria

Candida albicans

Tubercule bacillus
Staphylococci

Origin of cells involved


in the immune response
Haemopoietic stem cell

Myeloid progenitor
Monocyte

Lymphocyte
progenitor

Macrophage

Basophil

Dendritic cell
Neutrophil

B cell
NK cell

Thymus
Mast cell

CD8
T cell

CD4
T cell

Plasma
cell

Eosinophil

3 Types of Actions of the Immune System


1. Mechanical
2. Non-specific (innate
immunity)
3. Specific ( adaptive immunity )

Overview of immune responses

Interactions between innate and


& adaptive immunity
1. Innate immunity => Ag presentation (by Dendritic cells)
2. Adaptive immunity => Ag recognition (by T & B
lymphocytes)

Evidence for the role of immune


system in tumor rejection
Spontaneous regression
Infiltration of tumors by
lymphocytes and macrophages
Regression of metastases after
removal of primary tumor
Regression after chemotherapy
Lymphocyte proliferation in
draining lymph nodes
Higher incidence of cancer after
immunosuppression/immunodefici
ency (AIDS, neonates, aged,

Association
Association between
between
immunodeficiency
immunodeficiency and
and
cancer
cancer
cause of
immunodeficiency
primary

(inherited)
immunodeficien
secondary
cy
(acquired)
immunodeficiency
malari
a
autoimmuni
ty

malignanc
y
lymphoma
s
lymphoma, cervical
cancer, liver cancer,
skin cancer, Kaposis
sarcoma.
Burkitts lymphoma
lymphom
a

Tumors
Tumors stimulate
stimulate an
an immune
immune
response
response

Animals
Animals can
can be
be immunized
immunized against
against
tumors
tumors

Immunity
Immunity is
is transferable
transferable from
from
immune
immune to
to nave
nave animals
animals

Tumor
Tumor specific
specific antibodies
antibodies and
and cell
cell
have
have been
been detected
detected in
in humans
humans
with
with some
some malignancies
malignancies

Etiology Of Tumor
1) Inherited :
Expression of inherited oncogene
e.g. viral gene incorporated into host gene
2) Viral:
- Human papilloma, herpes type 2, HBV, EBV (DNA)
- Human T-cell leuckemia 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

Tumor Associated Antigens


!) Viral Antigen :
a- Viral proteins and glycoproteins
b- New antigens produced by virally infected host
cells under control of viral nucleic acid
2) Tumor specific antigens :
- Tumor cells develop new antigen specific to
their carcinogens
3) Tumor specific transplantation antigens :
- Tumor cells express new MHC antigens due to
alteration of normally present MHC antigens

Tumor Associated Antigens


4) 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

Immunity
Immunity against
against
tumor
tumor
All
All components,
components, specific
specific and
and
nonspecific,
nonspecific, humoral
humoral and
and
cellular
cellular affect
affect tumor
tumor progression
progression
and
and growth
growth

Antigens expressed on
tumor cells

Major Histocompatabili
Complex antigens
TST
A
TATA
TSTA

Tumor-specific
transplantation Ag
Tumor-associated
transplantation Ag

: unique to a tumor
Play an important role in tumor rejection.
TATA : shared by normal and tumor cells
Tumor-associated developmental Ag (TADA)
Tumor-associated viral Ag (TAVA)

Tumor
Tumor associated
associated transplantation
transplantation
antigens
antigens:: shared
shared Ag
Ag on
on virally
virally induced
induced tumors
tumors

Discovery
Discovery of
of tumor
tumor specific
specific
transplantation
transplantation antigens,
antigens, TSTA
TSTA

Tumor-Associated Developmental Ags

Found on cancer cells and on


fetal cells.
Do not trigger anti-tumor
immunity.
Used in diagnosis.
Alpha-fetoprotein(AFP)
Cancers of liver
Carcinoembryonic Ag (CEA)
colorectal cancer

Escape
Escape from
from
immunosurveillance
immunosurveillance

Lack of
Neo-antigens

Escape
Escape from
from
immunosurveillance
immunosurveillance

Lack of
Neo-antigens

Escape
Escape from
from
immunosurveillance
immunosurveillance

Lack of
class I MHC

Escape
Escape from
from
immunosurveillance
immunosurveillance

Tumors secrete
Immunosuppressive
molecules

Escape
Escape from
from
immunosurveillance
immunosurveillance

Tumors shed their


neo-antigens

Tumors may fail to express costimulatory


molecules involved in T cell activation.

Class I MHC

tumo
r
B7

tumor
Ag

CD28
CTL

Tumors escape the action of CTL by not expressing B7 which


provides 2nd signal involved in T cell activation

Utility of Immunology
in
Cancer Treatment

Use of tumor associated


antigens
Raise monoclonal antibodies
Use antibodies for diagnosis
Use antibodies for therapy

Stimulate the in vivo specific


response
Specific active treatment
Specific passive treatment
Adjuvant therapy to augment
specific immunity

Use
Use of
of tumor
tumor associated
associated antigens
antigens
monoclonal
monoclonal antibodies
antibodies

Monoclonal
Monoclonal antibodies:
antibodies:
use
use as
as aa diagnostic
diagnostic tool
tool

Immunotherapy
Immunotherapy of
of tumors
tumors
active immunotherapy
specific

killed tumor cells, purified or


recombinant Ag

nonspecifi
c

BCG, Propionibacterium acne,


levamisole, etc.

nonspecific
specifi
c

passive immunotherapy
LAK cells,
cytokines
antibodies alone or conjugated
with other agent, activated T
cells

Non-specific
Non-specific immunotherapy
immunotherapy
BCG, P. acnes,
muramyl
dipeptide
pyran, poly I:C

bacterial
products

activate macrophages
and NK cells (via
cytokines)

synthetic
molecules

interferon production

cytokines
IFN-, IFN-, IFN-, IL2, TNF-

activate macrophages
and NK cells

Cytokine
Cytokine immunotherapy
immunotherapy
IFN
IFN

remission of hairy
cell leukemia,
weak effect on
carcinomas
remission of
ovarian carcinoma

IL-2

remission in renal
cell carcinoma and
melanoma

TNF

reduction in
malignant ascites

increased expression
of class-I MHC,
possible anti tumor
effect
increased expression
of class-I MHC, Tc
and NK cell
activation
T cell proliferation
and activation, NK
cell activation
macrophage and
lymphocyte
activation

Active Immunization: The host


actively elicits an immune
response.
Specific
Vaccination with viral Ags: e.g.
Hepatitis B virus
Human Papilloma virus (HPV)

Thank You