Lecture 11

Cancer starts with

uncontrolled growth of 1 cell

Coley’s Toxin

Successfuly injected streptococcal organisms into patient with inoperable cancer and tumour disappeared

Limitations of surgery

• not possible to target all tumours

• can be disfiguring

• cancer can spread via blood and lymph systems

Limitations of radiation

• only effective if cancer is localized

• can burn and scar

• can cause death

Chemotherapy

chemical that can travel in body and destroy tumour

limitations of chemotherapy

• few chemicals specific for cancerous cells

• can cause secondary cancers

Cause of cancer: chemicals

• smoking

Cause of cancer: genes

• hereditary cancer incidence

• ex. BRCA1 mutation

Oncogenes

gene that cause cancer

dysregulation of oncogenes and tumour suppressor genes

can cause a cell to become cancerous

Her2

protein that can caue breast cancer cells to grow quickly

Herceptin

monoclonal antibody that binds to Her2 and blocks its signal to keep cells growing and increases ability of immune system to eliminate Her2+ cells

Why is cancer still very prevalent

• high mutation rate resists chemotherapy

• not all mutations drive cancer: difficult to identify essential genes

Aspects of immune system that can fight cancer

• vaccination

• treatment with monoclonal antibodies

Stephen Rosenburg

• showed that lymphhocytes from respected melanomas can be expended in vitro and transferred back into patients, which can elicit tumour regression

Co-stimulation

When T cells are activated by DCs, TCR engagement must occur

• second co-stimulatory signal from via CD80 and CD87 on DCs bind CD28 on T cells for full activation

• CD80 and CD86 also bind CTLA4

CTLA4 signalling

limits T cell proliferation and activation

limits IL-2 production

Blocking CTLA4 in tumour with monoclonal antibodies

limits tumour growth

Cancer immunity cycle

release of cancer cell antigens → cancer antigen presentation → priming and activation → trafficking of T cells to tumours → infiltration of T cells into tumours → recognition of cancer cells by T cells → killing of cancer cells

Cancer immunity cycle cont.

Accumulation of activated T cells in and through stroma → interaction with immune cells → maintained effector state and function