TUMOR IMMUNOLOGY

TUMOR ANTIGENS
Has tumor cell antigen ? The variety of tumor antigens ? The relationship between tumor antigen and carcinogenesis. What is tumor marker ? May tumor antigen stimulate Immune Responses ? Evasion of immune responses by tumor cells.

GENERAL FEATURE OF TUMOR IMMUNOLOGY

Tumor express antigens that are recognized as foreign antigen by the immune system. Immune respons frequently fail to prevent the growth of tumor. The immune system can be activated by external stimuli to effectively kill tumor cells.

1.Product of mutated oncogenes and tumor suppressor genes

Cell Membrane Tumor Antigens which related to carcinogenesis.
Ras

Carcinogen

Oncogens & Tumor Supp Genes (mutation)

Myc p53,

2.Product of other mutated genes

Tumor antigens which not related to carcinogenesis
TSTAs

Cell Membrane

Carcinogen

Other genes (random mutation)

3.Abberantly Expressed Normal Cellular Genes

Tumor antigens (Normal protein but inappropriate expression)
Tyrosinase MAGE

Cell Membrane

Gene Mutations Carcinogen

4.Tumor Antigens Encoded by Genome of Oncogenic Viruses

Cell Membrane Tumor antigens (Foreign antigens)
EBNAs(6) LMPs(2)

Oncogenic Viruses (EBV,HPV)

Viral Genes

VCAs

5.Oncofetal Antigens
Tumor antigens:
Normal protein in high level during development (fetal) AFP

Cell Membrane

Carcinogen

Silenced Normal Genes

CEA

6.Altered Glycoprotein & Glycolipid Antigens.

Tumor Antigens:
abnormal form of GP & GL and/or higher than normal level. GM2,GD2&GD3 CA-125,CA-19-9

Cell Membrane

Genes mutations Carcinogen

MUC-1

7.Tissue Spesific Differentiation Antigens

Tumor Antigen: Cell Membrane
normally produced by differentited cells

CD-10(CALLA) CD-20

Normal Genes Carcinogen

TUMOR ANTIGENS
Carsinogen treatment
genetic alterations ( gene amplification,deletian & translocation) expression of altered protein,glycoprotein & glycolipid (antigen) in tumor cells.

TUMOR ANTIGENS
1. Tumor antigen recognized by immune system which may stimulate the immune responses (Macrophage, NK Cells, Antibody and T cells). to kill tumor cells.(Immunosurveilance theory)

TUMOR ANTIGENS
Immune responses

Mcell

NKcell

Tcell

AB

antigen

antigen

TUMOR CELLS

TUMOR ANTIGENS
2. Tumor antigen could not be recognized as foreign by immune system but spesific for particular tumor. TUMOR MARKER DIAGNOSE AND THERAPY

TUMOR ANTIGENS
ANIMAL Antigen Antibody

Diagnose & Therapy

TUMOR CELLS

Function of Tumor Antigens

Antigens Immune Respone Diagnose Therapy

1. Product of mutated oncogenes and tumor suppressor genes. 2. Product of other mutated genes 3. Abberantly expressed normal cellular proteins. 4. Tumor antigens encoded by genomes of oncogenic viruses. 5. Oncofetal Antigens. 6. Altered glycolipid and Glycoprotein Antigens 7. Tissue Spesific Differentiation Antigens.

No
Yes Yes Yes No

Yes
No Yes Yes Yes

Yes No Yes Yes No

Yes
No

Yes
Yes

Yes
Yes

IMMUNE RESPONSE TO TUMOR

1. Macrophage
2. Natural Kiler (NK) Cell .
3. Cytolytic T Lymphocyte

4. Helper T Lymphocyte
5. Antibody

Macrophage
1. Phagocytosis
Lysozymes

Lysis of tumor cells

Tumor cells Macrophage Tumor cells

2. Production of Cytokine TNF(Tumor Necrocis Factor).

A.
Tumor Cell

B.
RA TNF

TNF

Thrombosis intravasculer Necroses of Tumor Cells

Apoptosis of tumor cells

Helper T Lymphocyte
Costimulator Macrophage (APC) MHC-II Tumor Antigens TCR Helper T Lymp (CD-4)

Production of Interferon-gamma Activation of Macrophage and NK Cells.

Activation of CTL

Production of TNF

Lysis of Tumor Cells

Apoptosis of Tumor Cells

Necroses of Tumor Cells

Cytolytic T Lymphocyte
A. Introduction of antitumor T cell response
Costimulator
Macrophage (APC) MHC-II TCR

T Lymp (CD-4)

Tumor Antigens

B. Effector phase of antitumor CTL response.

Tumor Cells Lysis of Tumor Cells

Helper factors

MHC-I

TCR

CTL (CD-8)

Tumor Antigens

Natural Killer (NK) Cells

= tumor antigen
NK Cells

No expression of MHC-I

Adhesion molecules

Tumor cells

Cytokines (IL-1,IL-12,INF-G)
NK Cells

Lysis of tumor cells

FcRes IgG
Tumor cells

(ADCC)

IgG antibody-coated tumor cells

ANTIBODY
= tumor antigen
antibody-coated tumor cells

ComIgG or IgM plement

Tumor cells

Lysis of tumor cells

NK cells/ FcRes IgG ADCC Macrophages
Tumor cells

IgG antibody-coated tumor cells

EVASION OF IMMUNE RESPONSES BY TUMORS

1. Class I MHC expression may be downregulated on tumor cells..

Tumor Cells MHC-I Lysis of Tumor Cells Tumor Antigens Tumor Cells TCR No Lysis of Tumor Cells No expression of Tumor Antigens TCR

CTL (CD-8)

CTL (CD-8)

3. No expression of MHC-II or costimulator

Costimulator Macrophage (APC) MHC-II Tumor Antigens Helper T Lymp (CD-4)

TCR

Production of Interferon-gamma Activation of Macrophages and NK Cells.

Activation of CTL

Production of TNF

Lysis of Tumor Cells

Apoptosis of Tumor Cells

Necroses of Tumor Cells

4. The produce of tumor may suppress antitumor immune response.

A. Introduction of antitumor T cell response
Costimulator
Macrophage (APC) MHC-II TCR

TGF-

T Lymp (CD-4)

Tumor Antigens

B. Effector phase of antitumor CTL response.

Helper factors

TGF-
Lysis of Tumor Cells

Tumor Cells MHC-I Tumor Antigens TCR

TGF-
CTL (CD-8)

5. Tumor antigens may induce specific immunologic tolerance.

Immune responses

Mcell

NKcell

Tcell

AB

antigen

antigen

TUMOR CELLS

6. The Cell surface antigens of tumors may be hidden from the immune system
(antigen masking, fibrin cocoon & antigenantibody complexs)
Immune responses

Mcell

NKcell

Tcell

AB

antigen

TUMOR CELLS

CONCLUSION
Tumor cells may express a variety of tumor antigens. Some of the tumor antigens may recognized as foreign by immune system. Tumor cells have abilities to escape from immune responses. Immune responses frequently fail to prevent the growth of tumor cells. Some of tumor antigens are usefull as tumor marker for diagnosis and therapy.

Recommended Text Book.

Abul K Abbas and Andrew H. Lichtman: BASIC IMMUNOLOGY 2nd ed, 2006-2007 Function and Disorders of the Immune System. SAUNDERS ELSEVIER

Recommended Text Book.

Abul K Abbas and Andrew H. Lichtman: BASIC IMMUNOLOGY 2nd ed, 2006-2007 Function and Disorders of the Immune System. SAUNDERS ELSEVIER