Cancer Immunology Flashcards
What is cancer? (1)
Hyper proliferation of cells
What is metastasis? (2)
Cells in tumour mass acquire capabilities in order to change morphology and move throughout body
What are oncogenes? (3)
Drive abnormal cell proliferation
As a consequence of genetic alterations that either increase gene expression or lead to uncontrolled activity of the oncogene regulation or oncogene encoded proteins
What are tumour suppressor genes? (3)
Under normal conditions they act to inhibit cell proliferation and tumour development
In many tumors, these genes are lost or inactivated, if you remove these negative regulators of cell proliferation they contribute to the abnormal proliferation of tumour cells
Genes whose normal function is control and inhibit cellular replication.
What is the two-hit hypothesis? (3)
Most tumor suppressor genes require both alleles to be inactivated, either through mutations or through epigenetic silencing, to cause a phenotypic change
What are the hallmarks of cancer devised by Douglas Hanahan and Robert Weinberg? (1)
Comprises six biological capabilities acquired during the multistep progress to cancer
Describe the 6 hallmarks of cancer (6)
Self-sufficiency in growth signals
Insensitivity to antigrowth signals
Evading apoptosis
Tissue invasion and metastasis
Limitless replicative potential
Sustained angiogenesis
What is tumour heterogeneity? (2)
Tumours are more than insular masses of proliferating cancer cells
Instead, they are complex tissues composed of multiple distinct cell types that participate in heterotypic interactions with one another
What are cold tumours? (3)
Exclusion of CD8+ T cells and NK cells from the tumour
Immunosuppressive immune cells in tumour
Poor prognosis and response to immunotherapy
What are hot tumours? (3)
CD8+ T cells and NK cells are present in the tumour
Suppression of immunosuppressive cell types
Improved prognosis and killing of tumour cells with immunotherapy treatment
What are the immunological problems with cancers? (2)
Tumour are self cells
Contain self proteins, whichif recognisedby the immune system would result in autoimmune disease
What are the red flags the immune system recognises? (3)
Integrated stress response - Increased replicationresults in transcription and translation of proteins and macromolecules at a faster rate than normal. A lot of incorrect folding and general mechanisms of a normal cell being done poorly
Increased replication results in the use of a lot of nutrients. Anaerobic and aerobic processes that are normally carefully regulated are altered resulting in different amounts of waste products
Increased replication results in cellular stress - Recognition of Stressed induced ligands
How are tumour cells able to hide from the immune system? (2)
By reducing the expression of MHC class I on their surface
No MHC class I means tumour specific T cells activity is reduced because your T cells cant recognize whether you are non self or not
How can natural killer cells recognise tumour cells? (2)
Recognise:
- reduced MHC class I
- stress induced ligand on surface
This induces activation of NK cells
What are NK cells? (1)
Cells that have evolved to recognise and kill targets without self MHC class I and with stress induced ligand
What is the aim of the immune system in the tumour microenvironment? (1)
Recognition of unregulated growth
What is the role of Damage Associated Molecular patterns (DAMPs) in the tumour microenvironment? (2)
Recognition of tumor - derived DAMPs usually initiates the activation of inflammatory signalling cascades to activate immune cells
Can also lead to sterile inflammation that can form a reinforcing loop of tumorigenesis.
What is the integrated stress response? (2)
Evolutionarily conserved intracellular signaling network
ISR aims to return of homeostasis or induce cell death
Describe the integrated stress response (3)
Activates the eukaryotic translation initiation factor eIF2
Triggers the translation of the key activating transcription factor ATF4 which is a multifunctional transcription regulatory protein that participates in a variety of cellular responses to different stresses or intercellular signaling molecules
Role of Transforming Growth Factor-beta in the tumour microenvironment (3)
Pleotropic inhibitory cytokine
Signals via SMAD dependent and independent pathways to transcription factors that functionally inhibit immune cell function
Role of Cyclo-oxygenase2 / Prostaglandin-E2
Inflammatory mediators in the tumour microenvironment (3)
Inflammatory mediators
Derived from Arachidonic Acid
Involved in homeostatic resolution of immune responses.
Role of Indoleamine 2, 3-Dioxygenase in the tumour microenvironment (2)
Function is to degrade tryptophan
W degradation products have immuno-inhibitory effects
Name the different immunomodulatory molecules in the gut (3)
Transforming growth factor beta
Retinoic acid
Interleukin 10
