15. Can the Immune System Fight Cancer? Flashcards
What are the potential mechanisms of the immune system to fight cancer?
Antibody + complement, Antibody-dependent cellular cytotoxicity (Ag on cell surface recognised Ab linked to K cell with FcR), direct NK cell cytotoxicity, cytotoxic T cells recognising tumour derived peptides presented by MHCI (to CD8+ TLC)
What is immune surveillance?
Cells of the immune system go around body looking for abnormal cells - if they are infected with virus or tumours
Which pathogens are closely linked to development of tumours?
If individuals have inherited/primary immunodeficiency: Epstein Barr Virus (causes lymphoma)
If individuals Immunosuppressed for organ transplants/AIDS: papilloma viruses (cervical/skin cancer), Hep B (liver cancer), Hep C (liver cancer), Herpes 8
If individuals infected with malaria: EBV (Burkitt’s lymphoma)
What cancer is Helicobacter pylori associated with?
Stomach cancer
What are the 5 groups of human tumour antigens?
- Tumour specific - Mutant p53
- Developmental - genes that tumours re-express - MAGE
- Viral - antigens from infectious agents expressed in tumour - HPV
- Tumour-Associated - present on tumour at similar levels (but may be present on normal cells also) - PSA (prostate specific antigen)
- Overexpressed - over expressed on tumour cells - Her-2 (Breast)
Tumour antigens may be present on the surface of cells (antibody attacked, NK, complement), or inside the cells (processed by MHC)
Why doesn’t the immune system attack most tumours (?
Tumours cell have developed techniques to reduce efficacy of immune system
- Antigens are initially expressed on tumour but one mutates to not express the antigen - immune system cannot see it anymore so cell will divide
- Secrete inhibitory molecules which down-regulate dendritic cell/cytotoxic T lymphocytes activity
- Regulatory T cells become stimulated but down-regulate activity of other immune cells
How do you activate T cells? How does it vary in tumours
Pathogen enters body, PAMPs and DAMPs recognised by PRRs on dendritic cells which sends signal to dendritic cell and tells it to up regulate CD80 and CD86 and provide potent co-stimulation.
Stimulation of TCR and co-stimulation (through CD28 on T cell being stimulated by CD80/86 on Dendritic cells)
With tumours there is a lack of co-stimulation so there is anergy (T cell becomes inactive/tolerant)
Vascular endothelial growth factor and IL-10 produced by tumour which promote tumour growth. TGFbeta also produced making more Tregs (and not as many killers)
What are TILs?
Tumour infiltrating lymphocytes (often regulatory T cells)
Why do tumour vaccines not work?
Tumour dampens down immune response due to loads of regulatory T cells
How may the immune system react to tumours if danger signals are present?
If a tumour occurs, the resting dendritic cells are exposed to danger signals (PAMPs or DAMPs) which activate dendrite cell and activate cytotoxic T cells
What is immuno-editing?
Loss of tumour specific antigens which leads to tumour escape from immune response
How may we persuade immune system to attack tumour (3)?
Antibodies - infuse someone with antibodies, or couple things onto antibody which would kill tumour cell (e.g. radioisotope)
Cell transfer - grow tumour specific T cells outside of body then infuse back into patient (so have many more cells which can attack tumour) (very good results), OR can add tumour antigen to cytokine which then is used mature dendritic cells outside of patient (then infused back into patient)
Vaccines - prophylactic (if virus associated cancers) or therapeutic (tumour antigens used to induce cytotoxic T cells)
