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Flashcards in L20 Deck (22)
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1
Q

What are 4 tumor-immunity reactions?

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

What are the 2 types of tumor antigens?

A

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
3
Q

How do CD8s recognize tumor cells?

A
  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
4
Q

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

A

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)

5
Q

How do NK cells recognize tumor cells?

A

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

6
Q

What is cancer immuno-editing?

A

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

7
Q

What are the 3 outcomes of immuno-editing?

A

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

8
Q

What are the 4 mechanisms of immune tolerance of cancer?

A
  1. Ignorance
  2. Deletion
  3. Anergy
  4. Suppression
9
Q

Explain ignorance.

A

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

  • ↓tumor antigens
  • ↓MHC
10
Q

Explain deletion.

A

Tumor apoptoses immune cells

- Tumor cells ↑Fas-ligand

11
Q

Explain anergy.

A

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
12
Q

Explain suppression.

A

Tumor cells using immune suppression mechanisms

  • ↑tumor inhibitory costim molecules, when bind T cells - inhibits them
  • Tumor derived immuno-suppressive factors
13
Q

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

A

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

14
Q

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

A

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

15
Q

What is the driver vs essential passenger mutation?

A

Driver = tumor growth & transformation

Essential passenger = mutation for tumor survival

16
Q

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

A

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

17
Q

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

A

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

18
Q

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

A

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
19
Q

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

A

Nonspecific actions –> not great efficacy

20
Q

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

A

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)

21
Q

How does radiation change the immune response?

A
Local radiation
↑SO proteins & inflam
↑DC uptake
T cell response 
Systemic response from targeted treatment
22
Q

What is a sign during treatment that might predict relapse?

A

Inflammation during treatment

Regression further into stem cell like properties