Flashcards in 4) Tumour Immunology Deck (17):
How can breast cancer be linked to the following symptoms: severe vertigo, unintelligible speech, truncal and appendicular ataxia?
Paraneoplastic cerebellar degeneration
What is the main difference between tumours and viral infections with regards to the immune response?
Viral infections trigger a lot of inflammation, which causes upregulation of costimulatory molecules so an immune response can take place
Tumours do not cause very much inflammation, especially early on so they are more likely to be missed by the immune system
What are the requirements for activation of an adaptive anti-cancer immune response?
Local inflammation in the tumour
Expression and recognition of tumour antigens
Which MHC class presents endogenous peptides?
MHC Class I
Give two examples of opportunistic malignancies.
EBV positive lymphoma (post-transplant immunosuppression)
HHV8 positive Kaposi sarcoma (occurs in HIV)
Give a few examples of viral infections that can cause cancer inimmunocompetent individuals.
HTLV1 associated leukaemia/lymphoma
HepB virus- and HepC virus-associated hepatocellular carcinoma
HPV positive genital tumours
Which oncoproteins of HPV are responsible for the induction andmaintenance of cervical cancer?
What proteins do the vaccines for HPV use?
Structural proteins are used to generate virus particles
Give an example of an HPV vaccine.
What are the two different times at which vaccines can be given?
Preventative vaccination (before the disease)
Therapeutic vaccination (try to control the disease once it has occurred)
Give examples of tumour-associated antigens.
Cancer-testis antigens – silent in normal adult tissues except male germ cells
MAGE – melanoma-associated antigens – identified in melanoma, also expressed in other tumours
PSA, PSMA, PAP,
When is p53 considered a tumour-associated antigen and when isit considered a tumour specific antigen?
Tumour-associated antigen – when it is over-expressed
Tumour specific antigen – when it becomes mutated
Describe the problem with tolerance in cancer immunotherapy.
T cells that react strongly with self are deleted (central tolerance) so most people have tolerance against tumour-associated antigens
What are the two major obstacles for the targeting of tumour-associated antigens in immunotherapy of cancer?
Autoimmune responses against normal tissues
What are three possible approaches to tumour immunotherapy?
Cancer vaccination – immunisation to stimulate natural anti-cancer responses
Genetic modification of T cells to express a receptor capable of recognising the tumour – these are then inserted back into the patient so that the T cells can kill the tumour cells
Blockade of molecules that inhibit T cell responses
Antibody based therapy
- bispecific antibodies
examples of tumour specific antigens
- epstein barr virus
- human papilloma virus
mutated cellular protein
- TGFbeta receptor 2
- Bcr - Abl mutation --> generates new proteins only found in cancer cells