lecture 29 - tumour immunology

Question 1

What are some ways that cancer develops?

Answer 1

Cells lose control of the cell cycle, causing abnormal growth
Abnormal activities of proto-oncogenes-RAS cell signaling and differentiation
Failure in tumout suppressing functions - P53 cell cycle
Defects in apoptosis gene - BAD regulator of programmed cell death

Question 2

How can DNA mutations or damage induce cell transformation

Answer 2

Chemicals, pesticides, radiation, viral infections

Virus DNA integrated into host cell genome

Question 3

What are tumour antigens

Answer 3

Neoplastic cells can express unique antigen that can be detected by lymphocytes
Antigen encoded by exclusively expressed tumour genes are tumour specific antigens (TSA)
Antigen is over expressed in in particular tumour (tumour associated antigen
Inappropriate expression of antigen that should normally be expressed at certain stages of development

Question 4

How does the innate immune system respond to cancer

Answer 4

Natural killer cells detect the lack of MHC expression
Mutations resulting in loss of NK cells activities are associated with certain cancers
Activated macrophages then secrete strong antitumor activity (TNF-alpha)

Question 5

How does the adaptive immune system respond to cancer?

Answer 5

Tumour infiltrating lymphocytes (TILS)
T cells → lack of T cells leads to increases in cancer
B cells generate antitumor antibodies against tumour specific antigen → tumour recognition and lysis

Question 6

What role do cytokines play in cancer

Answer 6

Interferons enhance immune anti tumour cell activities
Type I IFN can induce tumour cell death
IL-12 activates strong Th1 and CTL responses

Question 7

Describe the immune response to cancer

Answer 7

Elimination → Equilibrium → escape

Question 8

How is chronic inflammation related to cancer?

Answer 8

Chronic inflammation → increase in cellular stress signals → increased rate of mutation in cells
Proinflammatory cytokines can induce cell proliferation (IL-6)
Inflammation is proangiogenic→ increase in BV growth → greater tumour cell invasion in surrounding tissues

Question 9

How do tumours evade immune activation

Answer 9

Mutations in genes for TAP and beta2 microglobulin → reduced MHC expression in tumour cells
Poor stimulatory signals provided by tumour cells → lack of proper second signal may lead to clonal anergy in T cells and immune tolerance to cancer cells
Inhibition of T cell activation due to programmed cell death expression of protein ligand 1 (PDL-1)

Question 10

What factors contribute to immunosuppression by tumours

Answer 10

Increase of T reg near tumour cells
Recruitment of myeloid derived suppressor cells in tumour areas
Soluble factors can suppress immunity such as TGF beta and IL 10

Question 11

Describe the mechanisms of immunotherapy

Answer 11

Tumour specific T cells expanded and reintroduced to patients using cytokines to overcome anergic states
Adoptive cellular therapy
Dendritic cell based therapy
DC pulsed with tumor antigen → vaccination with tumour antigen pulsed dendritic cell → incico CD8 T cell → activation of tumour specific cell
Plasmid expressing cDNa encoding tumour antigen → vax with DNA or transfected dendritic cell → APC producing tumour antigen → activation
Blocks DNA synthesis and cell division
Targeted therapies
Induce or enhance antitumor activity