Exam 3: Dr. Pharr Cancer Immunity

Question 1

What are the 3 phases of tumor growth?

Answer 1

Elimination phase
Equilibrium phase
Escape phase

Question 2

What is the elimination phase?

Answer 2

Tumor cells removed by a combination of innate and adaptive immunity

Question 3

What is the equilibrium phase?

Answer 3

Tumor cells persist

The immune system prevents the spread of tumor cells

Question 4

What is the escape phase?

Answer 4

Tumor cells spread into the tissue

Development of new variants, immunosuppresssive environment around the tumor

Question 5

Describe thee three phases of tumor growth

Answer 5

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

Question 6

What tumor antigens are recognized by the immune system?

Answer 6

Tumor-specific antigens

Tumor associated antigens

Question 7

What are tumor specific antigens?

Answer 7

Mutated self antigens expressed in tumor cells, not found in healthy cells
The mutations could alter the function of the gene product

Question 8

What are tumor associated antigens? Examples?

Answer 8

Self antigens that are over-expressed in tumor cells
Prostate cancer: Prostatic acid phosphatase
Melanoma: tyrosinase

Question 9

Describe tumor specific and tumor associated antigens

Answer 9

Can be expressed by the same cell

Both are surface expressed and internal proteins

Question 10

How is adaptive immunity activated?

Answer 10

Tumor cell necrosis

Question 11

Where does tumor cell necrosis occur?

Answer 11

In an environment of low oxygen and nutrient starvation

Question 12

What does tumor cell necrosis result in?

Answer 12

The release of common intracellular proteins such as heat-shock proteins (Hsp70) and high mobility group proteins (HMGB1)

Question 13

What are intracellular proteins recognized by?

Answer 13

TLR on macrophages and immature DCs

Question 14

What are tumor antigens presented by?

Answer 14

DC expressing the costimulatory molecule B7

Question 15

How do intracellular proteins cause inflammation?

Answer 15

Function as DAMPs
HMGB1 binds TLR4
Hsp70 binds TLR2 and TLR4

Question 16

What happens to complexes of tumor antigens and heat shock proteins?

Answer 16

They are taken up by dendritic cells and presented to T cells

Question 17

How are tumors eliminated by innate immunity?

Answer 17

NK cells and γδ T cells: recognition of MHC class I related chain (MIC) by innate lymphocytes expresssing the activation receptor NKG2D

Question 18

What causes MIC expression?

Answer 18

Cell infection
Proinflammatory cytokines
DNA damage

Question 19

How are tumors eliminated by adaptive immunity?

Answer 19

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

Question 20

What does the secretion of IFN-γ do?

Answer 20

Increase MHC expression
Inhibit angiogenesis
Induce apoptosis of some tumors

Question 21

What do tumor specific antibodies do?

Answer 21

Recognize surface-expressed tumor antigens

Antibody-dependent cell mediated cytotoxicity by MK cells

Question 22

How do tumors evade immune elimination?

Answer 22

Avoid immune recognition

Suppress the immune response

Question 23

Describe how tumors avoid immune recognition

Answer 23

Genetic instability can result in a loss of tumor-specific antigens, reduced expression of MHC, reduced expression of MIC

Question 24

Describe how tumor suppress the immune response

Answer 24

Regulatory T cells have a cell-surface expression of CTLA-4, which produces IL-10 and TGF-β1