Download Tumor Immunology

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 system
Virus
Parasites
is to protect from: Tapeworms
Influenza
Polio mellitus
Malaria
Helminths
Fungi
Bacteria
Candida albicans
Tubercule bacillus
Staphylococci
Origin of cells involved in
the immune response
Myeloid progenitor
Haemopoietic stem cell
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/immunodeficiency (AIDS,
neonates, aged, transplant patients)
Association between
immunodeficiency and cancer
cause of immunodeficiency
malignancy

primary (inherited)
immunodeficiency
lymphomas

secondary (acquired)
immunodeficiency
lymphoma, cervical cancer,
liver cancer, skin cancer,
Kaposi’s sarcoma.

malaria
Burkitt’s lymphoma

autoimmunity
lymphoma
Tumors stimulate an immune
response
Animals can be immunized against tumors
Immunity is transferable from immune to
naïve animals
Tumor specific antibodies and cell have
been detected in humans with some
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 against tumor
All components, specific and
nonspecific, humoral and cellular affect
tumor progression and growth
Antigens expressed on tumor cells
Major Histocompatability
Complex antigens
TSTA
Tumor-specific
transplantation Ag
TATA
TSTA : 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-associated
transplantation Ag
Tumor associated transplantation antigens:
shared Ag on virally induced tumors
Discovery of tumor specific
transplantation antigens, 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)
Carcinoembryonic Ag (CEA)
Breast cancer  CA 15-3
Ovarial cancer  CA 15-5
Cancers of liver
colorectal cancer
Escape from immunosurveillance
Lack of
Neo-antigens
Escape from immunosurveillance
Lack of
Neo-antigens
Escape from immunosurveillance
Lack of
class I MHC
Escape from immunosurveillance
Tumors secrete
Immunosuppressive
molecules
Escape from immunosurveillance
Tumors shed their
neo-antigens
Tumors may fail to
express costimulatory
molecules involved in T cell activation.
tumor
Class I MHC
B7
CD28
tumor Ag
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 of tumor associated antigens
monoclonal antibodies
Monoclonal antibodies:
use as a diagnostic tool
Immunotherapy of tumors
active immunotherapy
specific
killed tumor cells, purified or
recombinant Ag
nonspecific
BCG, Propionibacterium acne,
levamisole, etc.
passive immunotherapy
non-specific
LAK cells, cytokines
specific
antibodies alone or conjugated with
other agent, activated T cells
Non-specific immunotherapy
bacterial products
BCG, P. acnes,
muramyl dipeptide
activate macrophages and
NK cells (via cytokines)
synthetic molecules
pyran, poly I:C
interferon production
cytokines
IFN-, IFN-, IFN, IL-2, TNF-
activate macrophages and
NK cells
Cytokine immunotherapy
IFN
remission of hairy cell
leukemia, weak effect
on carcinomas
increased expression of
class-I MHC, possible anti
tumor effect
IFN
remission of ovarian
carcinoma
increased expression of
class-I MHC, Tc and NK
cell activation
IL-2
remission in renal cell
carcinoma and melanoma
T cell proliferation and
activation, NK cell
activation
TNF
reduction in malignant
ascites
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