Helen rimmel tumour Flashcards
Recall the 4 points used for evidence that the immune system surveys for tumour presence
- 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
NKSc DCs Macrophages
Recall 2 problems with the body’s immune surveillance for tumours
- 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
- 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
PSA HER2 MAGE (melanoma) MUC-1 (many) CEA (should be foetal, expressed in tumours)
How might the tyrosinase enzyme be used in cancer immunotherapy, and what are its side effects
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
Herceptin
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?
Cost
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)
