Exam 3: Dr. Pharr Cancer Immunity Flashcards
What are the 3 phases of tumor growth?
Elimination phase
Equilibrium phase
Escape phase
What is the elimination phase?
Tumor cells removed by a combination of innate and adaptive immunity
What is the equilibrium phase?
Tumor cells persist
The immune system prevents the spread of tumor cells
What is the escape phase?
Tumor cells spread into the tissue
Development of new variants, immunosuppresssive environment around the tumor
Describe thee three phases of tumor growth
When tumors arise in a tissue, a number of immune cells can recognize and eliminate them
Variant tumor cells arise that are more resistant to being kiled
Over time a variety of different tumor variants develop
Eventually, one variant may escape the killing mechanism, or recruit regulatory cells to protect it, and so spread unchallenged
What tumor antigens are recognized by the immune system?
Tumor-specific antigens
Tumor associated antigens
What are tumor specific antigens?
Mutated self antigens expressed in tumor cells, not found in healthy cells
The mutations could alter the function of the gene product
What are tumor associated antigens? Examples?
Self antigens that are over-expressed in tumor cells
Prostate cancer: Prostatic acid phosphatase
Melanoma: tyrosinase
Describe tumor specific and tumor associated antigens
Can be expressed by the same cell
Both are surface expressed and internal proteins
How is adaptive immunity activated?
Tumor cell necrosis
Where does tumor cell necrosis occur?
In an environment of low oxygen and nutrient starvation
What does tumor cell necrosis result in?
The release of common intracellular proteins such as heat-shock proteins (Hsp70) and high mobility group proteins (HMGB1)
What are intracellular proteins recognized by?
TLR on macrophages and immature DCs
What are tumor antigens presented by?
DC expressing the costimulatory molecule B7
How do intracellular proteins cause inflammation?
Function as DAMPs
HMGB1 binds TLR4
Hsp70 binds TLR2 and TLR4
What happens to complexes of tumor antigens and heat shock proteins?
They are taken up by dendritic cells and presented to T cells
How are tumors eliminated by innate immunity?
NK cells and γδ T cells: recognition of MHC class I related chain (MIC) by innate lymphocytes expresssing the activation receptor NKG2D
What causes MIC expression?
Cell infection
Proinflammatory cytokines
DNA damage
How are tumors eliminated by adaptive immunity?
CD4 effector helper T cells: a. Required for protective antibody responses
b. Required for activation of naive CTL
c. Macrophage activation–production of reactive oxygen species at the tumor
CD8 cytotoxic T cells:
a. CTL-mediated killing of tumor cells
b. Secretion of IFN-γ
What does the secretion of IFN-γ do?
Increase MHC expression
Inhibit angiogenesis
Induce apoptosis of some tumors
What do tumor specific antibodies do?
Recognize surface-expressed tumor antigens
Antibody-dependent cell mediated cytotoxicity by MK cells
How do tumors evade immune elimination?
Avoid immune recognition
Suppress the immune response
Describe how tumors avoid immune recognition
Genetic instability can result in a loss of tumor-specific antigens, reduced expression of MHC, reduced expression of MIC
Describe how tumor suppress the immune response
Regulatory T cells have a cell-surface expression of CTLA-4, which produces IL-10 and TGF-β1
