Cancer Immunity

Question 1

Elimination phase

Answer 1

Tumor cells removed

- combo of innate and adaptive immunity

Question 2

Equilibrium phase

Answer 2

Tumor cells persist

- immune system prevents spread of tumor cells

Question 3

Escape phase

Answer 3

Tumor cells spread into tissue
- development of new variants, immunosuppressive environment around the tumor (when the tumor becomes clinically apparent)

Question 4

Tumor growth mechanisms

Answer 4

When a 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 killed –> over time a variety of different tumor variants develop –> one variant may escape the killing mechanism, or recruit regulatory cells to protect it, and so spread unchallenged

Question 5

Tumor specific antigens

Answer 5

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

Question 6

Tumor associated antigens

Answer 6

Self antigens that are over-expressed in tumor cells

• reactivation of embryonic genes not normally expressed in differentiated cell
• overexpression of normal self protein by a tumor cell changes density of self peptide presentation, allowing recognition by T cells
• ex: prostate cancer (prostatic acid phosphatase), melanoma (tyrosinase)

Question 7

TSA and TAA are expressed ____

Answer 7

By the same cell

- both surface expressed and internal proteins

Question 8

How is adaptive immunity activated?

Answer 8

Tumor cell necrosis

Question 9

Tumor cell necrosis

Answer 9

• occurs in an environment of low oxygen and nutrient starvation
• results in release of common intracellular proteins such as heat-shock proteins (Hsp70) and high mobility group proteins (HMGB1)
• recognized by TLR on macrophages and immature DCs

Question 10

Tumor antigens will be presented by ___

Answer 10

DC expressing costimulatory molecule, B7

Question 11

How do intracellular proteins cause inflammation?

Answer 11

Function as DAMPS

• HMGB1 binds to TLR4
• Hsp70 binds TLR2 and TLR4

Question 12

Activation of enzymes in response to severe cell stress

Answer 12

• destabilization of cell membrane and plasma membrane of tumor cell = sterile inflammation, proinflammatory
• tumor cell antigens are released with DAMPS, still not enough to activate DC, must be additional signals that separate tumor cell necrosis and healthy cell apoptosis

Question 13

Immunogenic cell death

Answer 13

Death of tumor cells by chemotherapy that generates an immune response, or cell death of cells that were not radiated by the therapy

Question 14

Elimination phase (innate immunity)

Answer 14

NK cells and gamma/delta cells

• recognition of MIC (MHC 1 - like) by innate lymphocytes expressing the activating receptor NKG2D
• MIC expression = cell infection, proinflammatory cytokines, DNA damage

Question 15

Elimination phase (adaptive immunity - CD4)

Answer 15

CD4+ effector helper T cells

• required for protective antibody responses
• required for activation of naive CTL
• macrophage activation: production of reactive oxygen species at the tumor

Question 16

Elimination phase (adaptive - CD8)

Answer 16

CTL mediated killing of tumor cells

- secretion of IFN-gamma (increase MHC expression, inhibit angiogenesis, induce apoptosis of some tumors

Question 17

Tumor-specific antibodies

Answer 17

Recognize surface expressed tumor antigens

- antibody dependent cell mediated cytotoxicity by NK cells

Question 18

Function of NK and gamma/delta T cells

Answer 18

• induce cell cytotoxicity

- secrete IFN gamma

Question 19

How do tumors evade immune elimination?

Answer 19

• avoid immune recognition

- suppress the immune response

Question 20

Avoiding immune recognition

Answer 20

Genetic instability

• loss of tumor specific antigens
• reduced expression of MHC
• reduced expression of MIC

Question 21

Suppressing the immune response

Answer 21

Tregs

- cell surface expression of CTLA-4, produce IL-10 and TGF-beta1