‫بسم هللا الرحمن الرحيم‬
•Cancer Origin and Terminology
•Malignant Transformation of Cells
•Oncogenes and Cancer Induction
•Tumor Antigens
•Immune Responses to Tumors
•Tumor Evasion of the Immune System
•Cancer Immunotherapy
•Cancer Origin and Terminology
•Malignant Transformation of Cells
•Oncogenes and Cancer Induction
•Tumor Antigens
•Immune Responses to Tumors
•Tumor Evasion of the Immune System
•Cancer Immunotherapy
•Cancer Origin and Terminology
•Malignant Transformation of Cells
•Oncogenes and Cancer Induction
•Tumor Antigens
•Immune Responses to Tumors
•Tumor Evasion of the Immune System
•Cancer Immunotherapy
Oncogenic Transformation of
Normal Cells
The transformation of normal cells into malignant cells:
Spontaneously arising transformants resulting from random mutations or
gene rearrangements during the normal processes of cell growth.
The action of carcinogens, which may be chemical, physical or viral in
nature.
Chemical Carcinogens
Physical Carcinogens
Viral Oncogenes
Cellular Oncogenes
•Cancer Origin and Terminology
•Malignant Transformation of Cells
•Oncogenes and Cancer Induction
•Tumor Antigens
•Immune Responses to Tumors
•Tumor Evasion of the Immune System
•Cancer Immunotherapy
Oncogenes in Tumor Development
Cancer-associated Genes
Process of Oncogenic Transformation
Model of sequential genetic alterations leading to metastatic colon cancer.
Each of the stages indicated is morphologically distinct, allowing for the
determination of the sequence of genetic alterations.
Immunotherapy
•Cancer Origin and Terminology
•Malignant Transformation of Cells
•Oncogenes and Cancer Induction
•Tumor Antigens
•Immune Responses to Tumors
•Tumor Evasion of the Immune System
•Cancer Immunotherapy
Tumor Antigens
1) Mutated Proteins
• oncogenic
- abnormal function: p53, p21Ras, βcatenin, CDK-4
- translocation: BCR-Abl (CML)
• secondary to genomic instability
2) Viral Proteins
• oncogenic
- EBV: EBNA1, LMP1, LMP2 (Hodgkin’s
disease, nasopharyngeal cancer)
- HPV: E6, E7 (cervical cancer)
3) Cancer-testes (germ cell antigens)
• expressed only in germ cells and tumors
• unknown function
- MAGE family: MAGE1, MAGE3, NYESO (melanoma, breast, glioma)
4) Differentiation Antigens
• overexpressed in tumor, but also
found in tissue of origin
- melanosomal proteins: tyrosinase,
gp100, Mart 1 (melanoma)
• unique to tumor
- rearranged Ig and TCR genes (B and
T cell lymphoma)
5) Overexpressed Oncogenic Proteins
• may reflect critical step in
oncogenesis
- WT1 -- regulates transcription
- MDM-2 -- blocks p53 function
- survivin -- inhibits apoptosis
- HER2/neu -- growth factor receptor
- Telomerase-- prevents senescence
Mechanisms for Generating Tumor-specific
Transplantation Antigens (TSTA) and Tumorassociated Transplantation Antigens (TATA)
Utilization of Antigens
􀂄 Techniques for defining tumor antigens
􀂄 Antigens purified from cancer cells and identified by
physicochemical techniques
􀂄 Tumor-specific T-cell clones tested against antigen negative cells
that express the antigen via transfection by plasmids
􀂄 Synthetic peptides constructed to precisely identify antigenic site
or epitope
􀂄 Immunodiagnosis
􀂄 TATA as useful tumor markers
􀂄 Released only from tumor tissue
􀂄 Specific for a given tumor type
􀂄 Detectable at low levels of tumor burden
􀂄 Has direct relationship to the tumor cell burden
􀂄 Present in all patients with tumor
􀂄 Tumors release antigen macromolecules that can be detected
in vivo and in vitro
Immunodiagnosis
􀂄 Examples of TATA used for markers
􀂄 Alpha-Fetoprotein
􀂄 Beta-subunit of human chorionic gonadotropin
(B-HCG)
􀂄 Prostate-specific antigen (PSA)
􀂄 CA 125
􀂄 Radio-labeled monoclonal antibody B72.3
􀂄 Carcinoembryonic Antigen (CEA)
􀂄 Protein-polysaccharide complex in colon
carcinomas
􀂄 Immunoassay can detect increased levels
in blood
􀂄 Specificity is low in certain cases, such as
heavy cigarette smokers and other cancers
Diagnostics

Ideal Tumor Marker
1. Specific for tumor type.
2. Released only in response to tumor.
3. Results proportional to tumor mass.
4. Quantitatively reflects tumor response.
5. Elevated with low tumor burden.
Prognostic roles of tumor
markers
AFP
CA125
CA153
CA199
CA72-4
CEA
CYFRA
21-1
★
Total
PSA
★
★
★
Islet cell carcinoma
★
uterine cervix
cancer
★
chorionic carcinoma
★
intestinal
carcinoma
★
★
esophageal
carcinoma
★
germinocarcinoma
★
hepatoma
★
★
SCLC
★
NSCLC
prostatic carcinoma
Free
PSA
★
breast carcinoma
pancreatic
carcinoma
NSE
CONCLUSION
cholangiocarcinoma
ovarian cancer
HCG
★
★
★
★
★
★
•Cancer Origin and Terminology
•Malignant Transformation of Cells
•Oncogenes and Cancer Induction
•Tumor Antigens
•Immune Responses to Tumors
•Tumor Evasion of the Immune System
•Cancer Immunotherapy
Host Immune Response to Tumor
Circumstantial and Experimental Evidence of a Host Immune Response to
Tumor
Circumstantial
Spontaneous regression
Regression of tumor after sub-lethal doses of chemotherapy
Regression of metastasis after resection of primary tumor
Mononuclear cell infiltration of tumor
High incidence of tumor after clinical immunosuppression
High incidence of tumor in immunodeficiency diseases
Increased incidence of tumors in aging
Experimental
Colony inhibition of tumors by sensitized lymphocytes
Lymphocyte blast transformation in presence of tumor extracts
Lymphocyte-enhanced cytotoxicity in patients with tumor
Macrophage-enhanced phagocytosis in patients with tumor
Tumor Immunology

Cancer immunosurveilance:
immune system can recognize and destroy
nascent transformed cells

Cancer immunoediting:
immune system kill and also induce changes
in the tumor resulting in tumor escape and
recurrence (epigenetic changes or
Darwinian selection)
•Cancer Origin and Terminology
•Malignant Transformation of Cells
•Oncogenes and Cancer Induction
•Tumor Antigens
•Immune Responses to Tumors
•Tumor Evasion of the Immune System
•Cancer Immunotherapy
•Cancer Origin and Terminology
•Malignant Transformation of Cells
•Oncogenes and Cancer Induction
•Tumor Antigens
•Immune Responses to Tumors
•Tumor Evasion of the Immune System
•Cancer Immunotherapy