Inflammation and Cancer

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Inflammation and Cancer

• Chen Dong, Ph.D
• Professor
• Department of Immunology
• 3-3263
• cdong_at_mdanderson.org

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Inflammation

• Inflammation is a general term for the local
  accumulation of fluid, plasma proteins, and whole
  blood cells
• Inflammation is initiated by physical injury,
  infection, or a local immune response.

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Types of inflammation

• Acute inflammation early and often transient
  episodes
• Chronic inflammation persistent infection or in
  autoimmunity.

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Inflammation during infection

• Deliver effector molecules and cells to sites of
  infection
• Provide a physical barrier preventing the spread
  of infection
• Promote the repair of injured tissue.

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Mammalian TOLL-like receptors
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TOLL-like receptor signaling
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(No Transcript)
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Antigen presentation Cellular immunity
TH1
IFNg
IL-12
Stat4 T-bet
IL-17 IL-17F IL-21 IL-22
IL-6 TGFb IL-23
CD28/ICOS
Inflammation
Naïve
TH17
Activated
STAT3 RORgt
IL-4
Stat6 GATA-3
IL-4 IL-5 IL-13 IL-10
Humoral immunity Allergy
TH2
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Anti-inflammatory cytokines

• IL-10
• IL-4

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Inflammation and cancer

• Viral infection and cancer HPV, HBV, HCV, EBV
• Bacteria Helicobacter pylori
• Non-infectious

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The evidence that links cancer and inflammation

• Inflammatory diseases increase the risk of
  developing many types of cancer (including
  bladder, cervical, gastric, intestinal,
  oesophageal, ovarian, prostate and thyroid
  cancer).
• Non-steroidal anti-inflammatory drugs reduce the
  risk of developing certain cancers (such as colon
  and breast cancer) and reduce the mortality
  caused by these cancers.
• Signalling pathways involved in inflammation
  operate downstream of oncogenic mutations (such
  as mutations in the genes encoding RAS, MYC and
  RET).
• Inflammatory cells, chemokines and cytokines are
  present in the microenvironment of all tumours in
  experimental animal models and humans from the
  earliest stages of development.
• The targeting of inflammatory mediators
  (chemokines and cytokines, such as TNF- and IL-1
  ), key transcription factors involved in
  inflammation (such as NF- B and STAT3) or
  inflammatory cells decreases the incidence and
  spread of cancer.
• Adoptive transfer of inflammatory cells or
  overexpression of inflammatory cytokines promotes
  the development of tumors.

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Dual roles of inflammation in cancer development

• Anti-tumor immunity
• Tumor-specific therapy
• Pro-tumorigenic effect
• Cytokines
• Growth and agiogenic factors
• MMPs

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Myd88 and intestinal cancers
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Overexpression of IL-23 in cancer
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Functional ablation of IL-23p19 signalling
restricts tumour growth.