L20 Flashcards
What are 4 tumor-immunity reactions?
- Immune suppresses tumor growth
- Adaptive immunity is responsible for tumor rejection
- Tumors inhibit T cells to survive
What are the 2 types of tumor antigens?
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
How do CD8s recognize tumor cells?
- Cross priming
Tumor ingested by APC (either b/c died or b/c PAMP)
APC (DC) activates CD4 - APC + CD4 @ lymph node
Provide all 3 signals needs to activate CD8 - Produce CD8 effectors
Require only 2 signals to kill cell in periphery
How do tumor cells recruit DCs to phagocytose them encouraging an immune response?
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)
How do NK cells recognize tumor cells?
Tumor ↓MHC to evade CD8
NK sees this & tumor stress signals
Or via ADCC if Abs against tumor cells exist
What is cancer immuno-editing?
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
What are the 3 outcomes of immuno-editing?
Elimination of cancer
Cancer equilibrium = cancer persistence and continued mutation
Tumor escape
What are the 4 mechanisms of immune tolerance of cancer?
- Ignorance
- Deletion
- Anergy
- Suppression
Explain ignorance.
Immune doesn’t see cancer, doesn’t know there is a problem b/c tumor:
- ↓tumor antigens
- ↓MHC
Explain deletion.
Tumor apoptoses immune cells
- Tumor cells ↑Fas-ligand
Explain anergy.
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
Explain suppression.
Tumor cells using immune suppression mechanisms
- ↑tumor inhibitory costim molecules, when bind T cells - inhibits them
- Tumor derived immuno-suppressive factors
What are the 2 ways you can overcome tumor immune evasion & immune tolerance?
Passive immunotherapy - give things to protect you from your tumor
Induce a host immune response
What are examples of passive immunotherapy? (Idea: giving patient things that will help fight against tumor cells)
+ NK/T cells against your cancer
Monoclonal Ab against the tumor
Cytokines
What is the driver vs essential passenger mutation?
Driver = tumor growth & transformation
Essential passenger = mutation for tumor survival
What kind of experiment would you design to generate a T cell response against a tumor?
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
What is CAR? How is it used as a cancer treatment?
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
What is the idea behind Ab based immunotherapy? What are 3 drugs for this purpose?
If tumor expressed TSA, you can give Abs the associated receptor to block signaling
- Cetuximab - vs EGFR, can’t bind EGF on tumor cells
- Trastuzmab - vs breast cancer, blocks Her2/neu receptor
- Rituximab - blocks CD20 receptor on B cells for B cell lymphoma
Why is cytokine therapy not a first choice of cancer treatments?
Nonspecific actions –> not great efficacy
Give an example of how cancer drugs can target co-signaling molecules between tumor cells and T cells. (anti-intuitive)
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)
How does radiation change the immune response?
Local radiation ↑SO proteins & inflam ↑DC uptake T cell response Systemic response from targeted treatment
What is a sign during treatment that might predict relapse?
Inflammation during treatment
Regression further into stem cell like properties
