Lecture notes from Imperial College London, Medical Biosciences BSc, 2nd year, Cancer Biology (CBIO) module.
Covers the main concepts related to cancer immunobiology, why cancer is not a simple disease for our intrinsic defences to defeat, which are the markers that characterise it, how viruses ...
Cancer Immunobiology
- immune system = organs, cells, processes that protect us against infections, illnesses & diseases
=> defence against ‘foreign’ invaders (bacteria, viruses, cancer?)
=> includes bone marrow, thymus, spleen, lymph nodes, WBCs...
2 responses: innate (rapid) - adaptive (slow)
- cancer treatments:
=> surgery: for early, localised cancer (often in combination with
systemic therapies (travels throughout entire body, seeking out cancer cells) for metastases)
chemotherapy, hormone therapy, immunotherapy...
=> radiotherapy (x-ray therapy): radiation to destroy cancer cells or impede their growth
=> external beam radiotherapy (through the skin)
=> brachytherapy (radioactive ‘seed’ implant in/ near tumour)
=> targeted therapy/ personalised medicine: target specific alterations/ mutations
=> small-molecule drugs or monoclonal antibodies that attach to specific antigens
=> chemotherapy: not curative used alone => in combination
=> immunotherapy: drug treatment so that immune system attacks cancer cells
Tumour cell antigen
- cancer cells express specific markers: tumour antigens (membrane p/ processed cytosolic p)
m (peptides, polysaccharides, lipids) recognised by the immune system & that triggers its response
=> demonstrated by transplantation tests in mice
=> different tumours = different antigens
, Discriminate tumour antigens
* TAA = TATA and TSA = TSTA
(T for transplantation)
W
Alt
*
as ↑
-- *
*
Y W
i
- types of tumour antigens (based on patterns of expression):
=> tumour-specific antigens (TSAs): only in tumour cells
=> mutation (radiation/ chemical carcinogens) => modified p => new tumour antigens
=> chemically-induced tumours express ≠ cell surface antigens
=> viral oncogenes => directly expressed/ integrated into DNA + expressed
=> virus-induced tumours express antigens encoded by virus => common
=> ex: HPV oncoproteins E6 and E7, mutated KRAS
=> tumour-associated antigens (TAAs): higher levels in tumour cells (but found in normal cells)
=> amplification (increased gene copies) caused by mutations, viral infection, genetic disorders...
=> altered glycosylation (post-translational modification where a carbohydrate is added)
=> ex: ERBB2, mesothelin, CD19
=> oncofetal antigens: inappropriately reactivated in tumour cells (normally only during foetal dvlp)
=> ex: carcinoembryonic antigen (CEA) in colon cancers, α-fetoprotein (AFP) in liver cancers
=> cancer/ testis antigens: inappropriately expressed (normally only in reproductive tissues)
=> ex: MAGE
How do viruses contribute to cancer?
- oncovirus: viruses that contribute to cancer (need a host cell to grow & reproduce)
=> 15-20% of human cancers associated with viral infections
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