Cancer and Immunotherapy Flashcards
what is a driver mutation
a change in a gene/protein that gives a cancer cell a fundamental growth advantage for its neoplastic transformation
what is a carcinoma
cancer derived form endoderm or ectoderm
what is leukemia
cancer of the blood or bone marrow
how is acute lymphocytic leukemia characterised
appearance of immature, abnormal B cell blasts
clinical effects of acute lymphocytic leukemia
anaemia, low WBC, weight loss, fatigue. thrombocytopenia
what are tumour associated antigens?
antigens derived from genes overexpressed in tumours, normal proteins minimally expressed by healthy tissues
what are tumour specific antigens
antigens restricted to tumours not found in healthy cells
what are oncofetal proteins
proteins normally expressed in fetal development not in adult tissue, re-expressed in some cancers
what are neoantigens
protein antigens encoded by mutated household genes
what are the products of mutated genes
chromosomal translocations
point mutations
neoantigens
example of oncofetal proteins
a fetoprotein - liver cancer
CEA - colon cancer
what are some oncogenic viruses
human T leukemia virus
EBV
HPV
Hep B and C
what cancers are caused by EBV
burkitts lymphoma and nasopharyngeal cancer
what cancer does hepatitis cause
liver cancer
what is the principal mechanism of recognition of tumour cells
CD8 CTLs
what do NK cells detect
decreased or lack of MHC class I
mechanism of killing cancer cells
Apoptotic cell death by:
antibody - ADCC
CTL recognition of virus peptides
NK - loss of MHC
what is anergy?
immunologic tolerance characterised by the failure to amount a full immune response to a tumour
how is an immuno suppressive environment established in cancer
adenosine released to suppress T cell activation
down regulation of MHC class I- failure to present cancer antigens
down regulation of tumour markers
failure of APC to present antigen
failure of CTLs and NK cell to kill
how is T cell activation repressed by tumours
adenosine released under hypoxic conditions
what immuno suppressive cytokines are released by tumour cells
IL10
TGFB
What are the new generation treatments for cancer
- monoclonal antibodies against cancer antigens
- cytokines - IL2, IF
- immune checkpoint inhibitors
- CART Cells
- cancer vaccines
what is important for diagnostic typing of cancer cells
all blast cells express a variety of lineage specific antigens
what are immune checkpoints
down regulate the response once an infection has been controlled
what are CART cells
combines the specificity of antibodies and cytotoxic ability of t cells
what are chimeric antigen receptors
molecules genetically engineered into a polyclonal T cell population - T cells recognise tumour antigens
what are the challenges in treating solid tumours with CART cells
identifying precise tumour antigen
improving filtration into
overcoming immunosuppressive environment
