Tumor Immunology II Flashcards
Eerst lecture Mandy, dan college II Sonja
What are the seven steps of the tumor-immunity cycle?
- Tumor ag release
- Ag-uptake by DC
- T-cell priming
- T-cell trafficking
- T-cell infiltration
- Ag-recognition
- Tumor killing
Why can T cells traffic into the tumor?
Because they are primed with tumor antigens
Name three examples how tumors can inhibit T cell killing
- Checkpoints presented in tumor tissues
- Thick stromal layer
- Inhibition of the number of DCs that present antigen in the LN
Name two ways by which antigen presentation by DCs can be enhanced to boost the anti-tumor immune response?
- In vivo targeting
- Adoptive transfer of ex vivo loaded and activated DCs
At which step of the tumor immunity cycle does DC-therapy interfere?
T cell priming in the LN
Why can DC-therapy lead to a more effective anti-tumor immunity cycle?
Because they are primed
What are ways to manipulate DCs in- or ex vivo? Administration of? (3)
- DC-activating factors
- DC-mobilizing agents
- Antigens/adjuvant
Why can we not make a vaccine based on the DC subsets that we isolate from the peripheral blood?
Only few DC subsets are present in the peripheral blood
Which cells are used for DC vaccines?
Monocyte-derived DCs
Which compound can be used to mature DCs?
Growth factors; GM-CSF
How long does it take to create one DC vaccine?
10 days
How are DCs loaded with antigens?
Antigen pulsing
What is meant with an “autologous setting” in DC vaccination?
You use tumor material from the mice/patient itself
What is meant with an “allogeneic setting” in DC vaccination?
Material that is used to load DCs is not genetically identical to the material that is present within the patient
Which allogeneic setting approach can be used for DC vaccine formation?
Tumor cell lines of multiple patients -> mix them
How can we further enhance DC-therapy efficacy? (2)
- Targeting TAM phenotype
- Combination with checkpoint blockade
What are TAMs?
Tumor-associated macrophages -> present within tumor tissue
Which phenotype are TAMs associated with?
Suppressive phenotype -> inhibit anti-tumor response
What are the three main mechanisms by which TAMs can inhibit the immune system?
- Direct suppression T cells
- Induce Tregs
- Inhibit DC maturation
What is the goal of using antibodies to block the PD1/PD1L axis?
Better activation and function of T cells
Why is the dogma that the PD1/PD1L axis is only important in the tumor site not really valid anymore?
Axis also present within the TDLN -> can hamper T cell priming by DCs
Which two in vivo DC targeting approaches did Sonja zoom in on in her second lecture?
- Synthetic long peptides
- mRNA vaccines
Why do you often need a proliferation step for immune monitoring of vaccine responses?
Often T cells in the blood are of low frequency
What are the different assay you can use for immune monitoring of vaccine responses? (4)
- IFNy ELISA
- IFNy ELISPOT
- Flow cytometry
- Changes in TCR clonality/diversity
