Flashcards
Week 6
Flashcards do conjunto (23)
- 1What are the 3 most common cancers in adults?-Lung
-Bowel
-Colorectal/breast - 2What are the 3 most common cancers in children?-Leukaemia
-CNS
-Neuroblastoma (aggressive) - 3What is the function of p53?-Inducing cell cycle arrest, senescence and apoptosis
-Responds to stress signals - 4What is p53 controlled by?-MDM2 targets p53 for ubiquitin-dependent degradation
-MDM2 modulates p53 transcriptional activity - 5Describe the feedback loop involving p53-p53 activates transcription of MDM2
-Increased expression of MDM2 (+MDM4) decreases p53 levels and inactivates it
-Further decrease in rate of MDM2 transactivation by p53 - 6What is ARF?-Tumour suppressor
-Interacts with MDM2 and inhibits p53 degradation - 7Describe elimination in terms of immunoeditingImmune-mediated destruction of most cancer cells
- 8Describe equilibrium in terms of immunoeditingThe immune response to enough to contain but not fully eliminate genetically unstable and mutating tumour cells
- 9Describe escape in terms of immunoeditingTumour cell variants selected in the equilibrium phase now grow out in an immunologically intact environment
- 10What does activation of T cells need?-TCR binding to MHC molecule with loaded antigen
-CD80/86 on APC binding to CD28 on T cell - 11What are some examples of tumour-associated antigens?-Mutated self proteins
-Over-expressed self proteins
-Lineage specific antigens
-Abnormal post-translational modification of self protein
-Viral proteins - 12What makes a good target antigen for tumour immunotherapy?-Tumour-specific (reduced toxicity)
-Widely applicable to patients with the same tumour
-Critical for tumour growth/survival
-Lack of immunological tolerance - 13What is the evidence for tumour protective immunity in humans?-Immunosupressed more frequently develop cancers (esp. virus-associated)
-Cancer patients develop spontaneous immune responses to their own tumours
-Presence of immune cells correlates with improved prognosis - 14How do tumours escape the immune response?-Loss of HLA class I (MHC) expression
-Reduced expression of other molecules involved in antigen processing/presentation
-Loss of co-stimulatory molecule expression (CD80/86)
-Loss of adhesion molecule expression
-Loss of target antigen
-T cell infiltration inhibition - 15Describe how immunosuppression at the tumour site occurs-TGF beta supresses anti-tumour T cell functions + induces Tregs
-IDO blocks CD8+ proliferation and promotes apoptosis of CD4+ cells
-Inhibition of dendritic cells (no APCs)
-FAS ligand, which kills T cells
-Recruitment of Tregs
-Myeloid-derived suppressor cells suppress T cell function - 16What triggers the non-specific T cell stimulation response to tumour cells?IL-2 (melanoma and renal cell carcinoma)
- 17How is it blocked? Treatment?CTLA-4 binds to CD80/86 suppressing the T cell
Ipilimumab is a CTLA-4 inhibitory (allows T cell to work) - 18What are the different vaccines for tumours made out of?-Tumour cells/lines
-Defined peptides/protein antigens
-Dendritic cell-based vaccines (DC taken from cells, loaded and put back in) - 19Describe adoptive T cell therapy Risks?-T cells are taken from donor
-Expansion of specific T cell populations occurs in vitro
-Infused into patient
Risk of graft vs. host disease - 20Describe TIL therapy-Tumour biopsy is taken
-Tumour-infiltrating lymphocytes are taken
-Infuse a high dose of such cells into the patients (partially eliminate own immune system first) - 21How can T cells be engineered for cancer therapy?-Find gene encoding for TCR
-Clone the gene
-Package into a retrovirus or into a cell
-Inject into patient - 22What is a consequence of immunotherapies?Autoimmunity
- 23Describe the mechanisms that monoclonal antibodies for cancer therapy use-Complement-mediated lysis
-Antibody-dependent cellular cytotoxicity
-Blocking receptor/ligand interactions
-Anti-angiogenesis
-Cytotoxic activity of conjugated antibodies
Informações
- Descrição
- Diagnosis and treatment of cancer Tumour immunology p53
- Criado por
- Dolu Falowo
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