L20

Question 1

What are 4 tumor-immunity reactions?

Answer 1

1. Immune suppresses tumor growth
2. Adaptive immunity is responsible for tumor rejection
3. Tumors inhibit T cells to survive

Question 2

What are the 2 types of tumor antigens?

Answer 2

TSA = tumor SPECIFIC antigens

• Only on tumor cells
• How immune can respond & reject tumor cells
  2. TAA = tumor associated antigens
• On both tumor AND normal cells
• Mutations that cause normal protein to be overexpressed or abnormally processed

Question 3

How do CD8s recognize tumor cells?

Answer 3

1. Cross priming
   Tumor ingested by APC (either b/c died or b/c PAMP)
   APC (DC) activates CD4
2. APC + CD4 @ lymph node
   Provide all 3 signals needs to activate CD8
3. Produce CD8 effectors
   Require only 2 signals to kill cell in periphery

Question 4

How do tumor cells recruit DCs to phagocytose them encouraging an immune response?

Answer 4

Send out danger signals - “I’m a stressed cell and am trying to survive when I shouldn’t be”
Express tumor associated antigens (MARG/MARI)

Question 5

How do NK cells recognize tumor cells?

Answer 5

Tumor ↓MHC to evade CD8
NK sees this & tumor stress signals
Or via ADCC if Abs against tumor cells exist

Question 6

What is cancer immuno-editing?

Answer 6

Tumor cells that escape immune detection grow into tumor mass
Idea that if a tumor survives in an immune competent person, it is going to be aggressive because it successfully evaded host mechanisms

Question 7

What are the 3 outcomes of immuno-editing?

Answer 7

Elimination of cancer
Cancer equilibrium = cancer persistence and continued mutation
Tumor escape

Question 8

What are the 4 mechanisms of immune tolerance of cancer?

Answer 8

1. Ignorance
2. Deletion
3. Anergy
4. Suppression

Question 9

Explain ignorance.

Answer 9

Immune doesn’t see cancer, doesn’t know there is a problem b/c tumor:

• ↓tumor antigens
• ↓MHC

Question 10

Explain deletion.

Answer 10

Tumor apoptoses immune cells

- Tumor cells ↑Fas-ligand

Question 11

Explain anergy.

Answer 11

Of T cells b/c (know there is a problem but can’t do anything about it)

• Lack co-stim molecules
• Not enough costim via APCs for priming

Question 12

Explain suppression.

Answer 12

Tumor cells using immune suppression mechanisms

• ↑tumor inhibitory costim molecules, when bind T cells - inhibits them
• Tumor derived immuno-suppressive factors

Question 13

What are the 2 ways you can overcome tumor immune evasion & immune tolerance?

Answer 13

Passive immunotherapy - give things to protect you from your tumor
Induce a host immune response

Question 14

What are examples of passive immunotherapy? (Idea: giving patient things that will help fight against tumor cells)

Answer 14

+ NK/T cells against your cancer
Monoclonal Ab against the tumor
Cytokines

Question 15

What is the driver vs essential passenger mutation?

Answer 15

Driver = tumor growth & transformation

Essential passenger = mutation for tumor survival

Question 16

What kind of experiment would you design to generate a T cell response against a tumor?

Answer 16

Sequence normal & tumor tissue
See differences in RNA sequences - find out the genes that are being actively expressed - which ones are unique to cancer
Develop anchor sequences for MHC expression that target those specific protein differences
T cell response

Question 17

What is CAR? How is it used as a cancer treatment?

Answer 17

Chimeric antigen receptor
Genetically modified T cells express this receptor so they respond better at tumor sites
- Infect T cells w/ virus expressing variable region of Ab specifically against tumor cells
- + T cell signaling components (cytokines)
- Transduce T cell
Used with leukemia/lymphomas

Question 18

What is the idea behind Ab based immunotherapy? What are 3 drugs for this purpose?

Answer 18

If tumor expressed TSA, you can give Abs the associated receptor to block signaling

1. Cetuximab - vs EGFR, can’t bind EGF on tumor cells
2. Trastuzmab - vs breast cancer, blocks Her2/neu receptor
3. Rituximab - blocks CD20 receptor on B cells for B cell lymphoma

Question 19

Why is cytokine therapy not a first choice of cancer treatments?

Answer 19

Nonspecific actions –> not great efficacy

Question 20

Give an example of how cancer drugs can target co-signaling molecules between tumor cells and T cells. (anti-intuitive)

Answer 20

Monoclonal Ab
Usually tumor cells interact with T cells and increase inhibitory signals via CTLA4
- CTLA4 (on antigen/DC normally) binds CD 28 (on T cell) with greater affinity that CD80 = activating signal
+ CTLA4 Ab –> block inhibitory signals
Same idea for PD1 (usually tissue signal to ↓T cell to ↓inflam)

Question 21

How does radiation change the immune response?

Answer 21

Local radiation
↑SO proteins & inflam
↑DC uptake
T cell response 
Systemic response from targeted treatment

Question 22

What is a sign during treatment that might predict relapse?

Answer 22

Inflammation during treatment

Regression further into stem cell like properties