Cancer immunology COPY Flashcards
IMMUNE INVOLVEMENT IN CANCER
i) what has the immune system evolved to protect against? (2) what can this result in in relation to tumours?
ii) higher incidence of cancer after which condition alludes to immne involvement in cancer development?
iii) the presence of which cells in the tumour/blood/LNs suggest a good prognosis in humans?
iv) the presence of which cells in tumours are a predictor of reduced survival?
v) is it possible for tumours to spontaneously regress?
i) immune sys has evolved to protect against MOs and self destruction by auto immune reactions
- can result in shielding of tumours from the immune system
ii) higher incidence of cancer after immunosuppression in AIDS and ageing
iii) presence of TILs > good prognosis
iv) presence of T regs > poor prognosis
v) cancers can sponataneously regress but this is rare
IMMUNE INVOLEMENT IN CANCER AS AN OLD IDEA
i) who noted tumour regression after infection?
ii) admin of which vaccine has been shown as an effective treatment for bladder cancer? how do the tumour cells respond to this? what happens as a consequence?
iii) which type of cells recognise MAGE-A1 - the first human tumour specific antigen?
i) william coley
ii) admin of BCG vaccine > taken ip only by bladder cancer cells > antigen pres on MHCII > immune cell recruit and cell mediated cytotoxicity of bladder cancer cells only
iii) Cytotoxic T cells recog MAGE-A1 tumour spec antigen
TUMOUR ANTIGENS
i) are TATA/TAAs unique to tumour cells? when are they normally expressed?
ii) are TSTAs unique to tumour cells? where are the genes encoding them specifically expressed?
iii) which type of antigen has antigens encoded by variant forms of mutated genes?
iv) which antigen may be expressed at low levels in normal cells but overexpressed in some tumours?
i) TATA are not unique to timoir cells - may be expressed during foetal development and at spec stages of differen
ii) TSTAs are unique to tumour cells and genes encoding them are specifically expressed by tumours
iii) TSTAs have antigens encoded by variant forms of mutated genes
iv) TATAs can be expressed at low levels in normal cells but over expressed in tumours
GENERATION OF TSTAs and TATAs
i) which process leads to the generation of a tumour specific neoantigen? which type of antigen is this
ii) which type of antigen may be due to expression of an oncofetal gene?
iii) which type of peptide may arise due to overexpression of normal protein on a cell?
i) neoantigen by mutation generating a new peptide on MHCI
- altered self peptide that is specific to the tumour cell TSTA
ii) oncofetal gene > inapprop expr of of embryonic gene (TATA)
iii) overexpression of normal protein > TATA
IMMUNE RESPONSES TO TUMOURS
i) name two types of cell that are involved in the innate response? are these MHC restricted?
ii) name three cells involved in adaptive response? are these MHC restricted?
iii) which three cytokines aid NK cell killing of tumour cells?
iv) which cells can infiltrate tumour masses and be anti or pro tumourigenic?
v) which cells produce a variety of cytokines to active other immune cells? which cells produce tumour specific antibodies?
i) innate - NK cells and macrophages (not MHC restric)
ii) adaptive > B cell, T helper and cytotoxic T cells
- these are MHC restricted
iii) NK cells kill tumour cells aided by IFNa, b and IL-2
iv) macrophages can infiltrate tumour masses (known as tumour assoc macrophages - TAM)
v) T helper cells produce lots of cytokines
- B cells produce tumour specific antibodies
CD8 T CELLS
i) what type of MHC do CD8 T cells recognise antigen on? what else is needed for activation?
ii) what does activation of the T cell result in production of? what does this drive?
iii) what can an effector T cell do upon antigen recognition? does this need co stimulation?
i) CD8 T cells recognise antigen presented on MHC I
- also need co-stim via CD80/CD86 molecules on APC (binded by CD28 on T cell)
ii) activation of T cell results in production of IL-2 which drives proliferation and differentiation into an effector/cytotox T cell
iii) effector T cells can recognise and kill infected cells upon antigen recognition - dont need co-stim as its an effector cell
CONTROL OF T CELL RESPONSES
i) what do inhibitory receptors expressed by T cells intefere with? what does this result in?
ii) name three inhibitory receptors expressed by T cells and what their ligand is
i) inhib receptors interfere with co stimulatory signals so it allows switching off of activated T cells
ii) CTLA-4 - binds B7 so it cant bind CD28 therefore T cell cant be activated
- PD-1 - ligand is PD-L1 (when PD1 binds PDL1 it makes the T cell inactive)
- FAS - ligand is Fas L
TUMOUR MICROENVIRONMENT
i) name three things it can comprise of? how do these interact with tumour cells?
ii) what effect may tumour derived anti inflammatory cytokines have?
iii) name a factor that can be secreted by the tumour and inhibit T cells directly?
iv) can a tumour change its microenvironment? what does the ME affect? (2)
i) can comprise of normal cells, molecules and blood vessels
- surround and feed the tumour cells
ii) tumour derived CKs can downregulate the immune response
iii) tumour can secrete TGFb/PD-L1 which can inhibit T cells directly
iv) tumours can change their ME and it affects how a tumour grows and spreads
MECHANISMS OF TUMOUR ESCAPE
i) what may the tumour reduce levels or completely remove so they cant be recognised by T cells? why cant T cells recognise these cells?
ii) what is an antigen loss variant?
iii) name two immunosuppressive factors that can be produced by the tumour?
iv) what can physically be done by the tumour to evade immune recognition?
i) tumour can reduce levels of MHC I so they cant be recog by T cells
- T cells cant recog cells with no MHC I as they are MHC restricted
ii) antigen loss variants - when some tumours stop expressing the antigens recognised by the immune system
iii) tumours can produce TGFb and PD-L1
iv) tumour can secrete factors to create a physical barrier to the immune system
UNDERSTANDING OF TUMOUR IMMUNOLOGY
i) what is cancer immunosurveillance?
ii) what is cancer immunoediting? what may this be due to?
iii) what are the three E’s of cancer immunoediting?
i) immunosurveillance > immune system can recognise and destroy emerging cancer cells
ii) immunoediting > immune system can kill cancer cells bit can also induce changes in the tumour resulting in tumour cell escape and further growth of tumour mass
- may be due to selection pressure of immune system on cancer cells
iii) elimination, equilibrium and escape
