tumor immunology Flashcards
Tumor
cells with uncontrolled cell growth
Cancer
when a tumor continues to grow and invade healthy tissue.
Oncology
the study of tumors
Benin tumors
localized, encapsulated, limited size
Malignant tumors
continue to increase in size, invade adjacent tissues
Metastasis
enter the circulation and spread
Carcinoma
endodermal/ ectodermal origin
Sarcoma
other cell types : mesodermal origin
Leukaemia
circulating cells of the immune system
Hematopoietic origin
Lymphoma
solid lymphoid tissue
Hematopoietic origin
Myeloma
bone marrow (plasma cell)
Hematopoietic origin
Metastasis
spread to distant organs
Normal Cell Growth promoting
Proto-oncogenes
Normal Cell Growth restricting
Tumor-suppressor genes
Molecular Basis of Cancer
Mutation of proto-oncogenes to oncogenes
Altered tumor-suppressor genes:
* p53 mutation
Colorectal cancer
successive mutations of several (5-6) independent genes
Burkitt’s lymphoma
Gene Translocation
Expression of MYC gene is altered
associated with a viral infection – Epstein Barr virus
Failure of the immune system ->
Tumor
What are tumor antigens
- Tumor Specific Antigens (TSAs)
2. Tumor Associated Antigens (TAAs)
Tumor Specific Antigens (TSAs)
found only on cancer cells
may arise due to:
- Mutation (Mutated P53)
- Viral antigens (ooncogenic viruses)
Tumor Associated Antigens (TAAs)
expressed only at certain stage of differentiation
or
Over expression of a normal antigen
Alpha-fetoprotein (AFP)
secreted by fetal liver
Carcino-embryonic antigen (CEA )
Found in the gut, liver and pancreas of fetus. Detected at low level in healthy adults
Cancer/testis antigen: (CT antigen)
expressed on immature sperm cells or trophoblasts ( in early embryo) but not is somatic cells
Melanoma-associated antigen (MAGE)
normally expressed on cells of testis (immunologically privileged site)
How Tumor Avoid Immune Attack
- MHC I down-regulated – loss of CTL (CD8)
- Antigen-less variants OR antigen variant (mutated)
- Antigen masking by sialic acid containing mucopolysaccharides
- Lack of co-stimulatory molecules (B7) – T cell anergy
- FasL expression – T cell apoptosis
- TGF-β production: suppress Th1 and promote T-reg
- Suppress the immune system by recruiting T-reg – which produce down regulating cytokines, TGF-β , IL-10
- Manipulating/ shedding – MIC (MHC I associated chain or Stress induced molecules (known as Killer activating ligand)
- Cancer of privileged sites
TGF-β, IL-10
suppresses auto-reactive T cells by TREG
High frequency of Treg
indicates a poor prognosis
Abnormally high level of monoclonal Ig
indicate a plasma cell tumor
Detection of alpha-Fetoprotein ( AFP)
associated with liver cancer
Carcinoembryonic antigen (CEA)
indicate malignancy – several, colorectal, pancreas etc
Prostate-specific antigen (PSA)
indicate prostate cancer
Cancer antigen -125 (CA-125)
ssociated with ovarian cancer, uterine (fallopian) tubes, endometrium (lining of the uterus), lung, breast, and gastrointestinal tract
Radiolabeled Monoclonal Antibody B72.3
recognizes all human carcinomas – used in tumor localization
IFN-alpha
NK cell activation
IFN-gamma
activates CTL, up-regulates MHC expression
IL-2
T cell, NK cell proliferation
Increasing co-stimulation
Anti-CTLA4 monoclonal antibodies
BCG – induce inflammation
bladder cancer therapy
Monoclonal antibodies
target the immunosuppressive mediators secreted by tumor
*** anti-TGF-beta
Anti-tumor monoclonal antibodies, with or without conjugation to toxic drug, radiation
immunotoxins
