Tumor

Immunopathology
T. Utoro
Department of Pathology
Gadjah Mada University School of Medicine

TUMS230210 1
 TUMOR IMMUNITY
Normal cell

Genetic alteration

Neoplastic transformation

Expression of surface antigens

Non-self antigen

Induce tumor surveillance

TUMS230210 2
 TUMOR IMMUNITY
Questions:
1. What is the nature of tumor antigens
2. What host effector systems may recognize
tumor cells
3. Is antitumor immunity effective against
spontaneous neoplasms
4. Can immune reactions against tumors be
exploited for immunotherapy

TUMS230210 3
 Tumor antigen
Tumor antigenicity is usually assessed by:
• The ability of an animal to resist a live tumor implant
after previous immunization with live or killed tumor
cells
• The ability of tumor free host animals to resist
challenge when infused with sensitized T cells from a
tumor-immunized syngeneic donor
• The demonstration in vitro of tumor cells destruction by
cytotoxic CD8+ T cells derived from a tumor-
immunized animal

TUMS230210 4
 Immunogenicity
of Tumors

The transplanted tumor is rejected

because of immunity acquired as a
result of the first tumor transplant.

TUMS230210 5
 Tumor antigen
Two broad categories:

TSAs (Tumor Spesific Antigens)

TAAs (Tumor Associated Antigens)

TUMS230210 6
 Tumor antigens
TSAs (Tumor Specific Antigens)
• Present only on tumor cells not on any normal
counterpart cells
• Derived from peptides that are uniquely present
within tumor cells and presented on the cell
surface by class I MHC molecules  evoke a
cytotoxic cell response
TAAs (Tumor Associated Antigens)
• Present on tumor cells as well as on some
normal counterpart cells

TUMS230210 7
 Tumor antigen
TSA (Tumor Spesific Antigen)
A. Tissue-specific shared antigen
B. Antigen resulting from mutation
C. Viral antigen
D. Other
TAA (Tissue Associated Antigen)
A. Tissue specific antigen
B. Overexpressed antigen
C. Oncofetal antigen
D. Differentiation antigen

TUMS230210 8
 Tumor Specific Antigens

A.Tissue-specific shared antigen

Encoded by genes that are silent in virtually all normal adult tissues
- but expressed in a number of tumors of various histologic types
- Testis (no HLA): the only normal organ in which MAGE protein are
present  cannot be expressed on their cell surface
TUMS230210 9
 Tumor Specific Antigens

B. Antigen resulting from mutation

• Mutated protooncogene and tumor supressor gene

• P53, K-ras, CDK4, bcr-c-abl
TUMS230210 10
 Tumor Specific Antigens

C. Viral antigens

• Antigens derived from oncogenic viruses

• E7 protein of HPV-16

TUMS230210 11
 Tumor Specific Antigens

D. Other Tumor Antigen

Mucins
• May give rise to tumor specific antigen: cancers derived
from pancreas, ovary, breast
• In the normal counterpart cells they (the epitopes) are
masked by carbohydrate
• Glycosylation of mucins  generate epitopes
• For practical purposes these antigens are TSA
• They are belong tu MUC-1

TUMS230210 12
 Tissue Associated Antigen

A. Tissue specific antigen

• Shared by tumor cells and their normal untransformed

counterparts
• Melanocytes and melanoma cells both express
tyrosinase
• Includes: MART-1, gp100, tyrosinase
TUMS230210 13
 Tissue Associated Antigens

B. Overexpressed antigen

C-erbB2 (neu): overexpressed in

30% of breast and ovarian cancer
TUMS230210 14
 Tissue Associated Antigens

C. Oncofetal antigens
Normally expressed in
embryonic tissue
• AFP: Alpha Fetoprotein
• CEA: Carcinoembryonic
antigen

TUMS230210 15
 Tissue Associated antigens

D. Differentiation antigen
• Peculiar to the differentiation state at which
cancer cells are arrested
• CD10 (CALLA – expressed by early B cell,
B-cell lymphoma and leukemia)
• PSA (Prostate Specific Antigen)
• β-hCG, expressed by syncitial trophoblast

TUMS230210 16
Antitumor Effector Mechanisms

ADCC

TUMS230210 17
Cellular effectors that mediate immunity
Cytotoxic T lymphocytes
• Protective role against virus-associated
tumors EBV, HPV (possessing MHC class 1)
Natural killer cells (NK cells)
• Lymphocytes capable of destroying tumor
cells without prior sensitization (after
activation with IL-2), including many that
appear non-immunogenic for T cells
Macrophages
ADCC

TUMS230210 18
 Inflammatory reaction is
correlated with better prognosis
In some tumors
• Medullary carcinoma of the breast
• Seminoma
• NPC
In general no clear correlation exist

TUMS230210 19
 IMMUNOSURVEILLANCE
Facts:
Increased occurrence of tumors
In immunodeficient host

Immunosurveillance
(it is not perfect)

TUMS230210 20
 Mechanisms to escape from
Tumor Immunosurveillance
1. Selective outgrowth of antigen-negative variants
2. Loss or reduced expression of histocompatibility
antigens (MHC I)
3. Lack of co-stimulation (CD80, CD86)
4. Immunosuppression
- oncogenic agent : ionizing radiation, chemicals
- tumor product : TGF-β
- immune response induced by tumor cells  activation
of suppressor T cells
5. Apoptosis of cytotoxic T cells

TUMS230210 21
TUMS230210 22
Mechanisms by which tumors evade the immune system
TUMS230210 23
TUMS230210 24