Tumor Immunology

1
Tumor Immunology

• Benign vs. malignant tumors
• Types of neoplasms
• Carcinomas
• the most common types of cancer arise from the
  cells that cover external and internal body
  surfaces. Lung, breast, and colon
• Leukemias/lymphomas ALL, AML, CLL, CML
• immature blood cells that grow in the bone marrow
  and tend to accumulate in large numbers in the
  bloodstream.(Uncontrolled mitosis in white blood
  cells)/ arise in the lymph nodes and tissues of
  the body's immune system.
• Sarcomas
• arise from cells found in supporting tissues.
  bone, cartilage, fat, connective tissue, and
  muscle.

2
(No Transcript)
3
(No Transcript)
4
(No Transcript)
5
(No Transcript)
6
Cell Transformation

• Characteristics
• Nutritional changes
• Lack of contact inhibition
• Immortality

7
Microscopic Appearance

• Cancer cells have Distinctive appearance
• a large number of dividing cells
• variation in nuclear size and shape
• variation in cell size and shape
• loss of specialized cell features
• loss of normal tissue organization

8
Chemicals and Cancer

• Mitogens
• Mutagens
• Carcinogens

9
Genes and Cancer

• Oncogenes viral
• Proto-oncogenes proteins
  involved in growth and cell-cell interactions
• Tumor Suppressor Genes Normal genes preventing
  cells from dividing and when mutated loss their
  functions and Cells divides Out of Control

10
Tumors and Viruses

• Hepatitis B liver cancer
• Human papilloma virus(HPV) cervical cancer
• Epstein Barr Virus Burkitts Lymphoma

11
(No Transcript)
12
Tumor-specific Transplantation Antigens

• Origin of TSTAs
• Point mutations
• Expressed by germ line cells
• Expressed by specific cell types
• Over expressed
• Post translation changes
• Viral oncogenes

13
(No Transcript)
14
Examples of tumor antigens
15
Examples of tumor antigens
16
Oncofetal Antigens

• Alpha fetoprotein (AFP)
• Carcinoembryonic antigen (CEA)

17
Discovery of Immune surveillance of tumors
18
(No Transcript)
19
Immune Response to Tumors

• Cells
• NK
• CTLs
• Macrophages
• Ab ADCC, Neutralization, CDCC, opsonization
• Cytokines
• Interferon
• TNF

20
Mechanism of Tumor Immune Escape

• Factors related to tumor cells
• Factors related to the hosts
• immune system

21
Factors related to tumor cells

• 1. low immunogenicity of tumor antigens and
  antigenic modulation
• 2. covering or blocking of tumor antigens on the
  surface of the tumor cells
• 3. Diminution or absence of MHC class I molecule
• 4. Lack of co-stimulatory molecule on the surface
  of tumor cells
• 5. Immune inhibitors secreted by tumor cells

22
Factors related to hosts immune system

• 1. Immunodeficiency
• 2. Suppressing immune function by tumor directly
  or indirectly

23
Mechanisms of Tumor evasion
24
(No Transcript)
25
The Strategies for Cancer Therapy

• The best scenario Kill all the tumor cells
  without destroy others in the body
• Surgery remove tumor cells tissues physically
  
• Radiotherapy non-selective, strong side effect
• Chemotherapy - non-selective, strong side effect
• Gene therapy relatively selective
• Targeted therapy - relatively selective
• Immunotherapy gt manipulate an immune response
  against tumor cells but not normal cells
• gt quite selective

26
Immunotherapy

• Anti-tumor mAb
• ADCC, Toxin conjugation, Radionuclide conjugation
• Passive Immunotherapy
• Adoptive cellular therapy
• cytokine therapy
• Enhancement of tumor immunogenicity
• Tumor vaccines

27
Tumor vaccines-Targeting DCs
28
Types of Tumor Vaccines
29
Enhancement of tumor immunogenicity
30
Immunotherapy with cytokine gene-transfected
tumor cells
31
Systemic cytokine therapy for tumors
32
Passive Immunotherapy for tumors
Adoptive cellular therapy
33
Therapy with Anti-tumor Monoclonal Abs
34
Approved Anti-tumor mAb