Tumor immunology -Thrush Flashcards
Mutations caused by what three things will be more likely recognized as foreign and destroyed?
- physical factors (UV light)
- chemical factors (nitrates, asbestos, nicotine)
- viruses (Epstein-Barr virus, HPV)
Why do cancers often have a lack of antigenicity? Why can this be a problem?
they are derived from the host.
the host has a more difficult time recognizing the cancer as being foreign and destroying it
How does the increase in gene expression lead to Burkitt’s lymphoma?
this is a mutation where c-myc is moved next to an IgH gene enhancer (constitutively expressed) leading to the over development of B cells–> lymphoma
How are T cells involved in the immune response to cancer cells?
There are TILs (tumor infiltrating lymphocytes) which are tumors which recruit T cells to them but then somehow suppress their activity once they are there
What are tumor-specific antigens?
unique to tumor cells (not on normal cells)
due to mutations that alter proteins.
these are rarely seen because tumor cells originate from normal tissue.
What are tumor-associated antigens?
tumor-associated transplantation antigens (TATA)
not unique to tumor cells .
usually proteins found on cells at different developmental stages (ex: fetal development) that will be expressed inappropriately high in tumor cells, or an over expression of a normal protein
ex: oncofetal genes
What are oncofetal antigens? What are 2 common oncofetal antigens?
expressed normally during embryogenesis and then disappear; re-expressed in some tumors
- Carcinoembryonic antigen (CEA)
found in some colon cancers (could be used to measure cancer burden) - Alpha-fetoprotein (AFP)
found in patients with liver and germ cell tumors (teratomas)
increased in hepatitis
increases in pregnancy – thought to play a role in maternal tolerance to fetus
after tumor therapy, increased levels = relapse of tumor
What are oncogenes?
abnormal regulatory genes/proteins found in some cancers of viral origin (oncogenic viruses)
protooncogenes – the normal cell counterpart of the oncogenes–> mutated protooncogenes can be mutated by viruses into oncogenes causing cancer
What are the tumor-related ways that tumors evade the immune system? (5)
- lack of antigenic epitope
- decreased MHC expression
- lack of co-stimulation
- production of inhibitory substances (ex: cytokines) by the tumor
- shedding of tumor antigens and tolerance induction
What are host-related defects that can lead to tumors not being recognized by the immune system?
- immune suppression
- defective T cells–> physical, chemical, viral agents or aging
- deficient antigen processing of tumor antigens
- failure of effector cells reaching the tumor or becoming activated
What are the common therapy methods for cancer?
first, conventional therapy to reduce cancer cell numbers (surgery, radiotherapy, chemotherapy)
then either passive immunotherapy to reduce the number of tumor cells
or (in the future) active immunotherapy to kill remaining cells
What does it mean to humanize an antibody?
in mouse produced antibodies, human Fc regions will be combined with them to reduce the amount of foreignness
What are the methods of passive immunotherapy?
monoclonal Abs to tumor specific antigens to:
- cause ADCC or C’ activation
- signal apoptosis
- prevent angiogenesis (tumors need blood to grow)
What are the methods of active immunotherapy?
-tumor infiltrating lymphocytes:
isolate “suppressed” lymphocytes (T cells) from the tumor site, stimulated them in vitro with IL-2, inject back into patient
-dendritic cells pulsed with tumor antigens: allows for better antigen processing/presentation and co-stimulation
-bone marrow transplant
can be useful for some tumors of lymphoid origin
-cytokines: to activate an immune response (“break” suppression)
-vaccination: Papilloma virus vaccine for cervical cancer
