L13-Tumour immunology

Question 1

What are three pieces of evidence for tumour protective immunity in humans?

Answer 1

• Immunosupressed individuals more frequently develop cancer
• Cancer patients can develop spontaneous immune responses to their own tumours
• Tumours with the presence of immune cells are associated with better prognosis

Question 2

What is cancer immunosureveillance?

Answer 2

The immune system can recognise the precursors of most cancers and can destroy them before they become clinically apparent.

Question 3

What is cancer immunoediting?

Answer 3

Sculpting of changing of the cancer by the immune system

Question 4

What are the three E’s of cancer immunoediting?

Answer 4

• Elimination - the majority of the cancer cells are destroyed by the immune system
• Equilibrium - the immune system and any cancer cell variant that has survived the elimination excist in dynamic equilibrium
• Escape - tumour cell variants now grow out in an immunologically intact environment.

Question 5

What two types of signals do t cells require for activation?

Answer 5

Both stimulation from the T cell receptor which binds to antigen peptides presented on MHC molecules, and co stimulatory molecules from the APC such as CD28

Question 6

What are the 5 main types of tumour associated antigens?

Answer 6

• Mutated self proteins e.g. from DNA damage
• Overexpressed self proteins
• lineage specific (differentiation) antigens
• Abnormal post translational modification of self protein
• Viral proteins e.g. HPV

Question 7

What would be 4 features of a good antigen for targetting in tumour treatment?

Answer 7

• Tumour specific
• Shared across many types of cancer
• Critical for tumour growth
• Does not develop immunological tolerance

Question 8

What are the 6 main mechanisms that tumour cells use to evade the immune system?

Answer 8

• Loss of MHC class 1 expression
• Loss of costimulatory molecule expression
• Loss of adhesion molecule expression
• Loss of target antigen
• Reduced expression of molecules involved in antigen presentation.
• Inhibition of T cell infiltration.

Question 9

How are regulatory T cells sometimes used by cancers to evade the immune system?

Answer 9

They are used by cancers to supress the surrounding cells to prevent T cell invasion

Question 10

What are myeloid derived supressor cells and what role do they play in cancer?

Answer 10

They are potent T cell function supressors that are upregulated by cancers.

Question 11

What are the three main methods for using T cells to treat cancer?

Answer 11

• Non-specific T-cell stimulation
• Vaccination
• Adoptive T cell therapy

Question 12

What is non specific T cell stimulation?

Answer 12

This uses immunostimulatory cytokines and also antagonistic antibodies to block immunological checkpoints (blocks coinhibitory receptor CTLA4). This promotes the immune system to attack cancer cells however only some patients respond and many reject it due to its toxic nature.

Question 13

How can vaccination be used to treat cancer?

Answer 13

Can inject irradiated tumour cells that are non proliferative to stimulate an immune response to them. This means an immune reaction to the cancer cells develops.

Question 14

What is adoptive T cell therapy and how is this used in cancer?

Answer 14

It involves transfusing whole t cell populations that are specific to the cancer cells.

Question 15

What are the two immune mediated and 3 direct effects of monoclonal antibodies on cancer?

Answer 15

Immune mediated:
-complement mediated lysis
-antibody dependent cell cytotoxicity
Direct effects:
-blocks receptor-ligand interactions
-anti-angiogenesis
-cytotoxic activity of conjugated antibodies