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Immunology 22 - Immunology 22-Cancer Immunology...

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Immunology 22-Cancer Immunology Inflammation may cause cancer Many chronic inflammatory diseases increase the risk of cancer at the side of inflammation IBD 10% develop colon/rectal cancer; Normal Population → 50: 100000 (0.05%) Reactive oxygen and nitrogen species can mutate DNA Many different ways that the immune system products can mutate DNA Inflammation, Infection and Cancer Chronic inflammation (infection or other) can lead to cancer; Helicobacter pylori→ stomach cancer Some viruses (oncovirus) directly cause cancer; Epstein-Barr virus, Kaposi’s sarcoma virus→ skin cancer, HPV→ cervical/ovarian cancer Infections may cause up to 25% of all cancers Vaccination against these viruses can prevent these cancers Human Papilloma Virus Vaccine Cervical cancer= 5 th most common cancer in women; incidence is 16: 100000 women; 250000 deaths/year HPV serotypes HPV-16, -18, -6 and -11 cause 90% of all cervical cancers; also cause anal, vaginal, penile, head, neck and oral cancers; some are gender specific Most cervical cancers are caused by HPV HPV Vaccines: 1. Guardacil= protects against HPV-16, -18, -6 and -11; consists of “empty” (no genome) virus-like particles containing HPV proteins; empty virus and adjuvant 2. Cervarix= protects against HPV-16 and -18; consists of L1 capsular protein from each serotype plus alum as an adjuvant About 80% effective in controlling persistent infection Inflammation and Tumour Progression Tumors use immune system to drive their own growth Tumours are chronically inflamed; lots of macrophage/neutrophils Influx of macrophage/neutrophils are important in tumour growth Tumour inflammation serves 2 purposes: 1. Drives angiogenesis to provide blood supply to the growing tumour 2. Creates a microenvironment which suppresses Th1 responses Angiogenesis is required for Tumour Growth Tumours need O2 and nutrients (therefore need blood supply) Requires immune cells; neutrophils drive angiogenesis; deleting neutrophils with Gr- 1 reduced availability of pro-angiogenic factor VEGF VEGF= growth factor for blood vessels Neutrophils drive angiogenesis through chemokine and growth factors; chemokines will attract endothelial cells into site; promote growth and survival Cytokines= VEGF, IL-12, IL-18, TNF Chemokines= Gro-1, MCP-1 Tumour Associated Macrophages
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Normal/inflammatory macrophage (M1)= phagocytic; produces TNFa, INFy, IL-12; ROS, RNS, proteases Alternatively Activated Macrophage (tumour associated macrophage; M2)= produced by tumours; important for normal healing process too; produces anti inflammatory cytokines (IL-10, TGF B) and chemokines that recruit neutrophils and for angiogenesis (CXCL1/2/3/8, VEGF, VEGA); recruited by monocyte which releases M-CSF, IL-4, IL-10 and IL-13; M2 produces growth factors and tissue repair factors; IL-10/TGFB suppress adaptive immune system ( encourage TH2 or Treg responses); increased IL-10= increased M2 macrophage and decreased M1 macrophage Inflammation can also kill cancer
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