Cancer Immunology

Question 1

Causes of mutagenesis and development

Answer 1

• spontaneous
• chemical carcinogens
• virus-induced (HepC, HPV)
• Immunosuppression
• Chronic inflammation
• UV/ionising radiation

Question 2

Cancer cells

Answer 2

• clonal mutations
• deregulated growth
• loss of tissue affinity
• resistance to apoptosis
• change in surface marker
• structural/biochemical changes
• development of tumour specific antigens

Question 3

Immune surveillance of cancer

Answer 3

• Proposed originally by Paul Ehrlich (1909)

- Refined by Burnet & Thomas (late 1950’s)

Question 4

How does the immune response control cancer?

Answer 4

Innate:
NK/ILC/MO/Neuts
Adaptive:
DC/CTL/BCell/Ab

Question 5

NK (natural killer cells) control of cancer

Answer 5

• NK look for changes in normal cells

- once activated, they can attack directly or alert other cells to danger

Question 6

Immune response-mediated tumour control stages:

Answer 6

1. Innate IR recognises tumour cell establishment
2. NK cells and other effectors recruited to site by chemokines, which also target tumour growth directly
3. Tumour specific T cells home to tumour site, along with macrophages and other effectors to eliminate tumour cells

Question 7

Immuno-editing eventually produces…

Answer 7

low antigenicity tumour cells

-pressure from immune system coupled with genomic instability selects for escape

Question 8

Immunoediting potentiates cancer progression

Answer 8

Elimination –>equilibrium–>escape

genetic instability/ tumour heterogeneity

Question 9

Development of clinical tumours

Answer 9

tumour establishment:

• Neovascularisation / neolymphogenesis (ANGIOGENIC SWITCH)
• influx of inflammatory cells
• changes to surrounding tissues

Question 10

Solid tumours consist of…

Answer 10

• cancer cells
• new vasculature
• macrophages
• Tregs
• altered stroma

Question 11

Primary tumour metastasis

Answer 11

• large tumours have disregulated vasculature - becomes hypoxic and necrotic
• many tumours can disperse to other sites - metastasis
• most frequent cause of cancer mortality

Question 12

Metastatic disease

Answer 12

• end point of carcinogenesis & loss of immune control
• primary tumours generally confined &therefore treatable by surgery whereas metastases are disseminated and systemic

Question 13

Immunotherapy of cancer

Answer 13

• non-specific therapies
• vaccination strategies
• cell-base therapies
• ANTIBODY THERAPIES

Question 14

Checkpoint inhibitors

Answer 14

• Trials in range of solid tumours show very significant benefits
• survival rates of 40-80% at 12-24 months
• lower toxicity than other therapies

Question 15

SNBTS

Answer 15

leading cellular therapies