Inflammation and cancer Flashcards
What is the resolution phase?
The loose of the signs of inflammation as damaged tissue is repaired and infection removed. There is no resolution phase in cancer.
Why has evolution not removed the ability of inflammation to cause cancer?
- protection from infection is more important so need an inflammatory response.
- Inflammation can also protect against cancer.
What type of inflammation causes cancer and how?
Chronic, by inducing tissue damage.
Who is a. the epithilium b. the endothelium c. fibroblasts and d. leukocytes involved in the whole tissue inflammatory response?
a. proliferated to repair the damaged barrier.
b. angiogenesis and vasodilation to improve blood flow, increased vascular permeability to provide serum/nutrients for repair.
c. repair the tissue structure, lay down the ECM.
d. detect damage/infection, initiate and direct type of response, destroy pathogen, regulate other tissue cells, stimulate repair and direct resolution phase.
Which two papers experiments with laser to study the immune response?
McDonald et al 2010: damaged liver and saw cells lost membrane integrity (red dye) and neutrophils migrating to the site of damage.
Lammermann et al 2013: skin damage, neutrophil migrated to the site, did not in the case of tumours which uses the monocytes to its advantage.
What are DAMPS?
damage-associated molecular patterns of alarmins from damaged/stressed cells.
What TLR stimulation induce?
Chemokines and cytokines, cell differentiation. requires MyD88 signalling.
What does PRR stand for?
Pattern recognition receptor.
How does the immune system respond to early tumours?
NK cells recognise and kill cells (relse IFN-gamma). these and other cells are recuited to the site by chemokines. Dentritic cells then take cancer antigens to the lymph nodes and T cells: cytotoxic t cell, Th1 CD4 helper cells. M1 macrophages also recruit to the site and help.
How do tumours evolve to avoid the immune reponse?
- increases the amount of regulatory T cells.
2. tailoring the inflamed stroma.
What are the 3 Es of tumour immunoediting?
Elimination, Equilibrium and Escape.
What are some current immunotherapies?
Prevention (vaccination, antibodies and DSAIDs), tumour killing antigens, reserving immunosuppression (monocloncal antibodies to free suppressed T cells, strong TLR stimulation, load pateints own dentritic cells with antibodies, cytokines and engineered cytotoxic T cells with CARs).
What is the evidence that chronic inflammation leads to cancer?
15-20% linked to preexisting infections or inflammations, persistent microbial infections. autoimmunity/chronic inflammatory diseases, studies of inflammation from known/unkown origins, NSAIDs reduce the risk of colorectal cancer. Animal models (initating mutation then inflammation get cancer, Apc model, needs MyD88).
What are the protumourgenic processes associated with inflammatory bowel disease? (8 answers)
Continuous damage and repair, hyperproliferating epithium, hypoxia disrupting DNA repair, MIF, cytokins and NO inhibiting p53 activity, mutagenic products from leukocytes (reactive oxygen and nitrogen intermediates, hydrogen peroxide), extensive angiogenesis, proteases remodelling the stroma, release of stroma growth factor store (cause angiogenesis and proliferation).
What is the evidence that cancer is associated with inflammation?
- inflammatory leukocytes are in all tumours from early stage.
- Tumours constitutively produce cytokines, chemokines, DAMPs and other proinflammatory molecules.
- The nature of the leukocytes/level or cytokine/chemokine production is a good prognostic indicator.
- oncogene activation can cause inflammatory responses.
- Targetting inflammatory mediators or their TFs reduces incidence and spread of cancer.
