Immunology 4: Tumour immunology and immunology of cancer

Question 1

Recall the 4 points used for evidence that the immune system surveys for tumour presence

Answer 1

1. Small tumours found at autopsy
2. Disease-free melanoma patients donating tissue
3. Increased cancer risk in the immunosuppresion
4. Men have higher risk of dying from cancer - women mount stronger responses

Question 2

Summarise the basis of immune-surveillance for malignancy

Answer 2

Tumour cell apoptosis –> antigen release –> APC action
T cells activated
“tumour-infiltrating lymphocytes” (TILs) proliferate an enter bloodstream
Cancer cell apoptosis

Question 3

Describe the selection pressure that is induced by the immune response to tumours

Answer 3

Good immune response to tumour cells by TILs favours cells that have a mutation that allows them to “hide” from immune system

Question 4

Describe the function of PD1-PDL1 interactions

Answer 4

Repeat exposure to an Ag causes T cell to express PD1
Tumour cell responds by upregulating PDL1
PD-1-PDL1 interactions decrease the T cell response

Question 5

How might the T cell response be boosted as an immune therapy for cancer?

Answer 5

PD1-PDL1 interaction blockade

Question 6

Recall the cell types involved in the innate response to a tumour

Answer 6

NKSc
DCs
Macrophages

Question 7

Recall 2 problems with the body’s immune surveillance for tumours

Answer 7

1. It takes a little while for the local inflammation in the tumour to be sufficient to produce a danger signal that provides costimulation for the adaptive immune response
2. Antigenic differences between tumour and self proteins may be very subtle

Question 8

Explain 2 ways in which immune responses to tumours have some similarities with those to virus infected cells

Answer 8

1. T cells can “see” inside cells and recognise TSAs

2. MHC displays contents of cell for surveillance

Question 9

What is a tumour-associated antigen?

Answer 9

Derived from a normal cellular protein
Aberrantly expressed
To recognise, tolerance must be overcome

Question 10

Recall 5 examples of TAAs

Answer 10

PSA
HER2
MAGE (melanoma)
MUC-1 (many)
CEA (should be foetal, expressed in tumours)

Question 11

How might the tyrosinase enzyme be used in cancer immunotherapy

Answer 11

It generally develops poor self-tolerance
It is expressed in many melanomas
Can direct immune response against it

Question 12

What are the 2 potential pitfalls of using TAAs in tumour immunotherapy?

Answer 12

AI responses to normal tissues

Development of tolerance

Question 13

Which proteins produced by HPV are oncogenes?

Answer 13

E6 and E7

Question 14

Recall a malignancy that is associated with immune suppression following transplant

Answer 14

EBV+ lymphoma

Question 15

Recall a malignancy that is associated with HIV

Answer 15

HHV8+ kaposi sarcoma

Question 16

Recall an example of using “naked” monoclonal antibodies in cancer therapy

Answer 16

Herceptin

Question 17

Describe the conjugated monoclonal antibodies used in cancer therapy

Answer 17

Antibody conjugated to cytotoxic drug

Question 18

Describe the bi-specific monoclonal antibodies used in cancer therapy and give an example of how this might work

Answer 18

GM to combine 2 specifities

Eg combining B and T cell specificity - used as a drug against B cell malignancy - drug crosslinks the T and B cells

Question 19

What is the main drawback of monoclonal antibody therapy?

Answer 19

Cost

Question 20

What is the only approved vaccination for cancer so far?

Answer 20

Advanced prostate cancer

Question 21

Describe how the anti-prostate cancer vaccination works

Answer 21

Remove patient’s WBCs
Stimulate them with a fusion protein between PAP and GM-CSF
DC maturation stimulated
PAP-specific T cell response stimulated

Question 22

What is the aim of immune-checkpoint blockade in cancer therapy?

Answer 22

Reduces the regulatory effect of existing T cell responses (eg tRegs)

Question 23

Recall and describe the pathways targeted by immune-checkpoint blockade

Answer 23

CTLA-4: expressed on activated tRegs, binds costimulatory molecules for APCs
PD-1: expressed on activated T cells, binds PDL1 to reduce T cell response
(perhaps panopto this)