LECTURE 13 (Cancer II)

Question 1

Why do immune responses often fail to check tumour growth?

Answer 1

Since tumours evolve in the host to evade immune recognition or resist immune effector mechanisms

Question 2

What are the different ways that Tumours evade immune response?

Answer 2

• Stop expressing the antigens that are targets of immune attack “Antigen loss variants”
  [if lost antigen is not involved in maintaining the malignant properties of tumour -> variant tumour cells continue to grow + spread]
• Tumours stop expressing class I MHC molecules -> cannot display antigens to CD8+ T cells
  [BUT NK cells are activated when target cells lack MHC I molecules -> NK cells can kill MHC I negative tumours]
• Secrete cytokines like TRANSFORMING GROWTH FACTOR β that suppress immune responses
• Express ligands for T cell inhibitory receptors such as PD-1 + induce low levels of B7 co-stimulators on APC resulting in binding of inhibitory receptors rather than stimulatory receptor
• Induce regulatory T cells -> suppress anti-tumour immune responses

NET RESULT IS REDUCED T CELL ACTIVATION

Question 3

What are the main strategies for cancer immunotherapy?

Answer 3

• To provide anti tumour effectors (antibodies and T cells) to patients
• Actively immunise patients against their tumours
• Stimulate the patient’s own anti-tumour immune responses

Question 4

What was the function of monoclonal antibodies against tumour antigens?

Answer 4

Antibodies bind to tumour antigens and either
- activate host effector mechanisms
- deliver toxins to tumour cells

Question 5

What is “Adoptive cellular immunotherapy”?

Answer 5

T cells contain tumour-specific CTLs (cytotoxic T lymphocytes) which find the tumour and destroy it

Question 6

Which immune cell is taken from individuals and grown to form tumour vaccines?

Answer 6

Dendritic cells

EXPLANATION: It is hoped that the dendritic cells bearing tumour antigens will mimic the normal pathway of cross-presentation and will generate CTLs against the tumour cells

Question 7

Which two vaccines are becoming remarkably effective?

Answer 7

• Hepatitis B virus (cause of liver cancer)
• Human papillomavirus (cause of cervical cancer)

Question 8

How do cytokines boost anti-tumour immune responses?

Answer 8

Treating patients with cytokines that promote lymphocyte activation

EXAMPLE: IL-2 enhances the numbers and functions of regulatory T cells which may interfere with anti-tumour immunity