Inflammation and cancer Flashcards
(23 cards)
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.
How does the cancer control the stroma?
- inflammatory inflitrations of leukocytes
- angiogenesis
- lymphogenesis.
- fibroblast differentiation
- reshape the ECM
- presence of cytokines, chemokines, MMPs and growth factors.
the ECM changes and tissue remodelling promotes invasion.
Give an example of an oncogene which causes cancer inducing an inflammatory response.
Ret in human papillary thyroid carcinoma. Chromosomal translocation, nessacry and sufficient, induces and transcribtional programme that causes inflammation.
Ras/raf path can induce cytokines/chemokines
Myc activation can induce chemokines to attract mast cells and IL1 beta to induce angiogenesis.
What are TAMs?
tumour associated macrophages.
How to M2 TAMs incourage tumourogenesis?
stimulate proliferation and angiogenesis, favour invasion and metastatsis,make immunosuppressive molecules (IL-10 and TGF-beta) Tumour bring in more M2 than M1. induce DNA damade via TNK causes ROS. produce VEGF. TNF and chemokine release drive protease production. MIF decreases p53 and apoptosis.
What do M1 TAMs do?
cytotoxic and recruit NK cells etc early in the immune response. release cytotoxic factor, phagocytose, release chemokines.
How to cancers switch the balance of TAMS to M2s?
- Tregs are abundant and release IL-10 to recruit M2s.
- Supress TH1 and CD8 T cells (M1s respond to Th1s).
(More Th2 cells and metastasis via M2s).
What do N1s and N2s do?
N1: tumour cytoxic, activate CD8 T cells, increase TNF alpha, ICAM-1 and FAS.
N2: protumourgenic (appear more circular) , increase arginase, CCL2 and CCL5.
Where are macrophages and neutriphils arisen from?
mylo-derived suppressive cells (MDSC)
