Immune evasion

Question 1

What are the 7 steps in tumor immunity cycle?

Answer 1

1. Release of cancer cell antigens (by cancer cell deaths)
2. Cancer antigen presentation (by dendritic cells/APCs)
3. Priming and activation (of APCs and T-cells)
4. Trafficking of T-cells to tumor
5. Infiltration of T-cells into tumor
6. Recognition of cancer cells by T-cells
7. Killing of cancer cells

Question 2

What are the two ways to kill cancer cells and how does it work?

Answer 2

1. Direct: immune cells use death receptors of cancer cells to kill (or release perforin and granzymes)
2. ADCC (anti-body dependent cell cytotoxicity): killing of anti-body coated cells by innate immune cells

Question 3

What are the 3 steps that lead to tumor escape?

Answer 3

1. Elimination: of cancer cells by immune cells
2. Equilibrium: between cancer cell death and replication
3. Escape: to many cancer cells

This happens through genetic instability of cancer cells and tumor heterogeneity which leads to immune selection of surviving cancer cells

Question 4

What are the 6 ways for tumor escape (intrinsic mechanisms)?

Answer 4

1. Loss of tumor antigen
2. Loss or dysfunction of antigen processing machinery
3. HLA class 1 antigen loss or down-regulation
4. Secretion of immune suppressive cytokines
5. Elimination of the direct killing pathway (shedding of Fas ligand)
6. Over-expression of anti-apoptotic protein

Question 5

What are the 3 “types” of tumors?

Answer 5

1. Hot (inflamed) tumor: normal
2. Cold (excluded tumor): T-cells stay in periphery of tumor and don’t go into tumor mass
3. Cold (ignored) tumor: immune cells ignore tumor because the don’t recognize it

Question 6

What macrophage conversion happens with tumor progression?

Answer 6

From M1 (activated and pro-inflammatory) to M2 (pro-tumor)

Question 7

How do Tregs contribute to tumor progression?

Answer 7

• Immunosuppressive cytokin production
• Direct effector T-cells lysis
• Support M2 macrophage formation
• Treg conversion and accumulation
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