Bui Lecture.pdf

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Inflammation = the influx of immune cells and production of cytokines into a specific location, often at the site of infection, a wound, or a tumor Immune cells = typically innate : macrophages, dendritic cells, neutrophils, mast cells? Eos? Non-immune cells = tumor cells, fibroblasts, “stroma” Cytokines, genes = NF-kB, IL-6, TNFa, Myd88
Evidence for inflammation induced cancer • Epidemiologic – Ulcerative colitis, a chronic inflammatory disease of the colon, is associated with 10x higher incidence of colon cancer – Aspirin reduces colon cancer risk by 22%; current guidelines do not recommend NSAIDs for cancer prevention – Hepatocellular carcinoma is associated with chronic hepatitis associated with HBV or HCV – Cervical cancer is associated with chronic infection/inflammation due to HPV – Gastric cancer is associated with chronic inflammation due to H. Pylori • Experimental – Mice that lack MyD88 and thus are deficient in TLR signals are resistant to colon cancer – Mice that lack NF-kB are resistant to colon cancer
Page 1 and 2: Tumor Immunology Jack Bui, MD, PhD
Page 4 and 5: Tumor immunology = the study of wha
Page 6 and 7: Immune cells function to eliminate
Page 8 and 9: Figure 15.12d The Biology of Cancer
Page 10 and 11: The birth of tumor immunosurveillan
Page 12: Paradigm shift : Cancers are opport
Page 15: Shankaran et al., Nature 2001 Mice
Page 18 and 19: The presence of tumor specific T ce
Page 20 and 21: Evidence for tumor immunosurveillan
Page 22 and 23: Shown is survival in ovarian cancer
Page 24: Endogenous T Cell Responses to Anti
Page 28 and 29: Goals 1. Present evidence that the
Page 30 and 31: Shankaran et al., Nature 2001 WT tu
Page 32 and 33: Cancer immunoediting: regressor tum
Page 35 and 36: Evidence for equilibrium • Human
Page 37 and 38: Melanoma complicating treatment wit
Page 39 and 40: Implications of equilibrium state
Page 41: Inflammation and Cancer: “Cancers
Page 45 and 46: Deletion of the NF-kB activator IKK
Page 47 and 48: Goals 1. Present evidence that the
Page 49 and 50: Evidence for Cancer Immunoediting:
Page 51 and 52: Normal cell Not recognized Induced-
Page 53 and 54: Gasser et al., DNA damage induces N
Page 55 and 56: Evidence for p53’s role in activa
Page 57 and 58: Corollary to Cancer Immunoediting:
Page 59 and 60: Passenger mutations leading to neo-
Page 61 and 62: Oncogene-driven models of cancer ca
Page 63 and 64: Goals for this hour 1. Present evid
Page 65 and 66: What cells/molecules promote vs inh
Page 67 and 68: Immune therapy of melanoma • IL-2
Page 69: Peripheral blood mononuclear cells
Page 74 and 75: An example of immunotherapy
Page 76 and 77: The presence of tumor specific T ce
Page 78: Can we remove immune suppression?
Page 81 and 82: Cancer immunoediting describes the
Page 83: Some major unanswered questions •

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