The Immune System and Cancer Flashcards
What are the three primary role of the immune system in the prevention of cancer?
Eliminate or suppress viral infectious to protect from virus induced tumours
Eliminate pathogens quickly so that an inflammatory environment (conductive to tumorigenesis) does not occur
Identify and eliminate tumour cells
What are the three stages of tumour immunoediting?
Elimination
Equilibrium
Escape
When there is incomplete elimination of tumour cells by the immune system an equilibrium can establish between the immune system and developing tumour. T/F?
True
What events occur within the tumour during the equilibrium period of immunoediting?
Tumour can continue to evolve, accumulating further changes that can modulate tumour-specific antigens and stress-antigens that they express in order to evade the immune system
The immune system acts as a selective pressure on cancer cells. T/F?
True
What happens in the escape phase of immunoediting?
Immune system is no longer able to contain tumour growth and a progressively growing tumour results
What cell functions are regulated by the RAS/RAF/MAPK pathway?
cell cycle regulation wound healing tissue repair integrin signalling cell migration expression of genes involved in the formation of new blood vessels
How does the Ras/Raf/MAPK pathway become activated?
EGFR or PDGFR bind to a protein tyrosine kinase receptor
After binding of EGFR to its receptor how does the Ras/Radf/MAPK pathway lead to activation of Ras?
EGFR becomes phosphorylated allowing docking of proteins such as GRB2 and SH2 to the activated receptor
This allows binding of SOS which promotes removal of GDP from Ras, which activates Ras
After activation of Ras how does the Ras/Radf/MAPK pathway progress?
Ras activates Raf kinase
Raf kinase phosphorylates and activates MEK 1 which phosphorylates MEK2 which phoshoylates MAPK
Active MAPK can then activate a number of molecules to cause changes in gene expression
What gene is responsible for making Raf protein?
BRAF gene
How can mutations in BRAF gene lead to cancer?
This can cause the Raf protein to be continuously active allowing the transmission of message to the nucleus even in the absence of chemical signals
this allows uncontrolled growth and division of cells
What is the most common mutation of the BRAF gene?
V600E mutation
What is the mechanism of action of vemurafenib?
Interrupts RAF/MEK step on the Ras/Raf/MAPK pathway to prevent cell growth and division
What type of cancer is vemurafenib most commonly used against?
Melanoma
Describe the immunotherapy which is used against bladder cancer?
Bacillus clamette-guerin a weakened form of bacteria which causes tuberculosis, inserted into the bladder by a catheter and causes an immune response against the cancer cells
Cytokine therapy can be used in the treatment of cancer. Describe how IFN alpha/beta affects cancer cells?
Promotes MHC Class 1 expression and cell division
Cytokine therapy can be used in the treatment of cancer. Describe how IL-2 affects cancer cells?
Promotes expansion of tumour specific T cells
How can monoclonal antibodies be used to combat cancer?
Specific antibodies which target cancer cells directly and mediate tumour destruction can be used
By what mechanisms can monoclonal antibodies kill tumour cells?
Induction of apoptosis
complement mediated cytotoxicity
Conjugated to toxin/isotope
Ipilimumab is a cancer therapy which blocks the CTLA4 antigen. What is the normal role of CTLA4?
It is an off switch for cell growth and division
When may CTLA4 by switched off physiologically?
In the gut when faced with a foreign ingested substance to prevent digestion of gut by lymphocytes
Describe how tumour cells use PDL1 to evade the immune system?
When PDL1 on cancer cells binds to PD1 on T cells this forms a biochemical ‘shield’ which protects the tumour cells from destruction and often causes apoptosis on the T cell
What are the available cell based therapies in the treatment of cancer?
Haematopoietic stem cells tumour infiltrating t cells dendritic cell vaccines Natural killer cells gamma delta t cells virus specific T cells genetically engineered T cells
