Immunology 4: Tumour immunology and immunology of cancer Flashcards Preview

MCD Y2: Immunology > Immunology 4: Tumour immunology and immunology of cancer > Flashcards

Flashcards in Immunology 4: Tumour immunology and immunology of cancer Deck (23)
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Recall the 4 points used for evidence that the immune system surveys for tumour presence

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


Summarise the basis of immune-surveillance for malignancy

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


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

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


Describe the function of PD1-PDL1 interactions

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


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

PD1-PDL1 interaction blockade


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



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

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


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

1. T cells can "see" inside cells and recognise TSAs
2. MHC displays contents of cell for surveillance


What is a tumour-associated antigen?

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


Recall 5 examples of TAAs

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


How might the tyrosinase enzyme be used in cancer immunotherapy

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


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

AI responses to normal tissues
Development of tolerance


Which proteins produced by HPV are oncogenes?

E6 and E7


Recall a malignancy that is associated with immune suppression following transplant

EBV+ lymphoma


Recall a malignancy that is associated with HIV

HHV8+ kaposi sarcoma


Recall an example of using "naked" monoclonal antibodies in cancer therapy



Describe the conjugated monoclonal antibodies used in cancer therapy

Antibody conjugated to cytotoxic drug


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

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


What is the main drawback of monoclonal antibody therapy?



What is the only approved vaccination for cancer so far?

Advanced prostate cancer


Describe how the anti-prostate cancer vaccination works

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


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

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


Recall and describe the pathways targeted by immune-checkpoint blockade

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)