Lecture 4- cancer immunology Flashcards
what are the characteristics of cancer?
-clonal, altered growth, resistance to control, structural and surface changes, altered affinity and tumour Ags
what is the role of the immune response?
innate = ILC/macrophages/neutrophils/DC
adaptive = DC/T cells/ B cells / antibody
how do you get protection via NK cells?
-NK look for changes in normal cells
-Once activated, they can attack directly or alert other cells to danger, primarily via IFN-gamma.
what are lymphocyte killing mechanisms?
Perforin / granzyme killing of target tumour cells
IFNg triggers cascade of effects including;
leukocyte recruitment
p53 upregulation
Angiogenesis
Macrophage activation
what is the concept of immunoediting?
Clear evidence that both the innate and adaptive immune response controls and eradicates nascent cancer cells.
“Immunoediting” eventually produces low antigenicity tumour cells by selection.
Pressure from immune system coupled with genomic instability selects for escape.
what are the 3 Es of immunoediting?
elimination, equilibrium and escape
why does size matter in cancer?
The growing tumour depends entirely upon development of new microvessels to suppy nutrients (neovascularization)
Therefore tumours need angiogenic factors (VEGF and chemokines) to allow development.
what is the path to metastasis?
Large invasive tumours have disregulated vasculature – becomes hypoxic and necrotic
Many tumours can then disperse to other sites – metastasis
what are the options for cancer treatment?
clinical cancer treated by immunotherapy, surgery or chemo
what is mutagenesis in cancer?
Genetic mutations not uncommon, but carcinogenic mutation rare
Multiple sequential mutations required to generate cell which is competent to initiate cancer
Generally require triggers for mutation
what is metastasis and morality?
Metastatic cancer represents the end-point of carcinogenesis and loss of immune control.
Primary tumours generally confined and therefore potentially treatable by surgery, whereas metastases disseminated and systemic.
Metastatic disease responsible for 90% of all death from cancer
why is metastasis hugely inefficient?
Models clarify define early events in metastasis
Process highly inefficient
Can be a long time between establishment of primary cancer and metastatic disease
what is the establishment of metastases?
Seed and soil –
some tissues supply a better environment for metastatic cancer cells to grow in.
Cancer Homing –
tumour cells are drawn specifically to certain tissues by “homing factors”
how are nascent cancers removed?
1 - Innate IR recognises tumour cell establishment
2 - NK cells and other effectors recruited to site by chemokines, which also target tumour growth directly.
3 - Tumour-specific T cells home to tumour site, along with macrophages and other effectors to eliminate tumour cells.
how much death does cancer cause in the UK?
Corresponds to ~30% all deaths
In numbers, 165,000 deaths per annum in UK
Each year 360,000 new cases diagnosed
What are the drivers of mutagenesis?
chemical carcinogens, virus induced, immunosuppression, spontaneous mutation, UV / ionising radiation, chronic inflammation
what is the metastatic pathway?
1- escape from iR
2 - Lymphogenesis angiogenesis
3 - altered cell adhesion
4 - tissue modulation
5 - migration
6 - homing
7 - establish at a new site
