BL- TUMOR IMMUNOLOGY Flashcards
immunodeficiencies (esp T cells) have inc rate of tumors
e.g. AIDS patients have a higher rate of Kaposi sarcoma, Burkitt lymphoma, and some other tumors.
Evidence for cancer immune surveillance:
Immune Surveillance
proposed in 1950 that the real role is to survey cells and kill abnormal guys, and this would kill cancer
We can think about the role of the immune system in neoplastic development as a series of stages in a process that has been called _____
“immunoediting”
Organ transplant recipients taking powerful immunosuppressive drugs had a 25 to 100-fold increase in tumors relative to healthy controls.
Evidence for cancer immune surveillance:
If ____ are invading cancer, better prognosis
lymphocytes
Nude mice (mice with no thymus) should get tumors very readily, but in fact spontaneous tumors are______
rare in these mice.
People treated with chemotherapy may have a 14-fold increased risk of developing secondary leukemia.
Evidence for cancer immune surveillance:
(NK) cells, which are not part of the traditional (T and B cell) immune system can:
tumoricidal
immunoediting
role of the immune system in neoplastic development as a series of stages
A small percentage of tumors, mainly melanomas and some lymphomas, spontaneously regress, presumably due to an immunologic response
Evidence for cancer immune surveillance:
IMMUNOEDITING STEPS
Elimination- kill the bad guy
Equilibrium
Escape: the tumor cells fight back
Driver mutation
a mutation that gives a selective advantage to a clone in its microenvironment, through either increasing its survival or reproduction.
creates cancer
Activated T cells that recognize tumor-associated antigens can easily be identified.
The presence of lymphocytes in a tumor (tumor-infiltrating lymphocytes or TIL,) many of which are tumor-specific, is a good prognostic sign.
Evidence for cancer immune surveillance:
lymphocytes infiltrate the tumor, but do not fully destroy it. Instead the tumor and lymphocytes exist in _______
Equilibrium
IMMUNOEDITING STEPS
when a clone becomes malignant its most likely fate is to be recognized as abnormal by both the innate and adaptive immune systems, and thus ______
eliminated
((IMMUNOEDITING STEPS))
tumors fight back when the immune system attacks them.
For example, it is common to find tumor-specific ______ surrounding tumor clusters in biopsies.
CTLs
Becomes tumors are out of control and mutating a lot, the immune system may:
have a hard time keeping up
allows escape
The tumor is invisible to the immune system or _____ it locally
suppress immune cells
leads to escape
______ probably the most important cells in tumor resistance.
CD8+ T cells (CTL)
Tumor Acs. Antigens
Different from normal cell by:
- over expression of normal Ag
- mutated
Th1 cells- CD4+ T cells
recognize the tumor antigens, make lymphokines, and attract angry M1 macrophages
Tumor rejection antigen
Antigen from a tumor that the immune system can “see”
usually called LGLs (large granular lymphocytes).
part of innate immunity.
Natural Killer (NK) cells
Cells need to see _____ to actually fight a tumor
Immuno-dominate epitope (if it exists, proposed)
ONCOFETAL ANTIGENS
Fetus grows a lot, may turn on again in adulthood but CAN BE turned back on into a cancer
VERY high false positive in screening
tumor-infiltrating lymphocytes (TIL)
Cells directly from the tumor
This technology utilizes cells from the patient’s immune system to destroy cancerous cells that cannot be surgically removed.
Cells isolated from the patient’s blood, tumor, or lymph nodes.
Adoptive cell transfer therapy.
DIFFERENTIATION ANTIGENS
Characteristic of a specific cancer
Monoclonal AB can target this and treat it
ex: HER-2/neu
Natural mechanisms to kill tumor cells
- CTL
- Th1
- Macs
- NK
- ABs
Vaccine to cancer
Every tumor is different, so making a vaccine is challenging
ex:
pts monocyte–> dendrytic cells–> soaked in prostate antigen –> used as vaccine
$$$
QALY
Quality adjusted life year
Ins companies will pay 30,000 per QALY
Innocent Bystander Cancer Rx
BCG (TB) is injected directly into the tumor.
A ferocious delayed-type hypersensitivity reaction to BCG ensues, and the tumor cells are killed as innocent bystanders.
treatment of choice for superficial bladder
carcinoma.
Check point inhibitors
“Off button” for immune cells (lymphocytes)
T cells:
CTLA-4
PD-1
B cells: CD80/86
Tumors are rich in ligands for these things
Monoclonal ABs can target this
