Tumour Immunology Flashcards
What is a hallmark of cancer?
The ability to evade immune destruction
What is immune surveillance?
A constant control and elimination of malignant cells by the immune system
How do normal cells become tumour cells?
In response to oncogenic stimuli (carcinogens, radiation etc) they transform into tumour cells
How is the cancer immunoediting process initiated?
The tumour cells’ expression of tumour specific markers and proinflammatory danger signals
What is cancer immunoediting?
1) Elimination
Innate & adaptive immunity eradicate the developing tumour
2) Equilibrium
If the elimination process is not successful, then the tumour cells may enter the equilibrium phase where they are either maintained chronically or they are immunologically sculpted by immune editors to produce new populations of tumour variants.
3) Escape
Where tumour variants evade the immune system and become clinically detectable
What is evidence for immune responses against tumour growth, that inhibit the tumour?
Lymphocytic infiltrates around some tumours
Enlargement of draining lymph nodes
= better prognosis
Evidence that the immune system protects against tumour growth
Immunodeficient individuals have an increased incidence of some types of tumours
Evidence for the fact that tumours evade immune surveillance by engaging inhibitory receptors on T cells
The therapeutic blockade of the T cell inhibitory receptors like PD-1 and CTLA-4 leads to tumour remission
Remission = a decrease in or disappearance of signs and symptoms of cancer
What is the principal mechanism of tumour eradication?
Killing by cytotoxic T cells, specific for the tumour antigen
How are CTL responses induced?
By the recognition of tumour antigens on host APCs
Tumour cells or their proteins are ingested by host DCs
Then they are processed and presented by the MHC class I (via cross-presentation)
Hence CD8+ T cells can be activated for targetted killing of the tumour cells
Are NK cells capable of killing tumour cells? If so, how?
Yes, they are!
When an MHC class I is missing, then that inhibitory signal is not present anymore & the NK cell can go & kill the tumour cell (it is getting its activation signals)
CD4+ anti tumour responses
Increased numbers of Th1 cells in the tumour infiltrates are associated with a good prognosis
Th1 cells work by activating macrophages
Are anti-tumour antibodies detectable in some cancer patients?
Yes
How and why are immune responses against tumours weak?
Tumours evolve to evade host immune recognition and resist immune effector mechanisms as:
Tumours elicit little inflammation
They downregulate antigen/MHC presentation:
There are mutations in the MHC genes/antigen processing which lead to a lack of T cell recognition, sometimes tumours fail to produce tumour antigen so it is not processed/presented
They promote immunosuppression:
Through the production of immunosuppressive proteins or the expression of inhibitory cell surface proteins, they inhibit T cell activation
Inhibition of T cell activation or differentiation into Th1 or CTLs
Tumours may create an immunosuppressive environment with regulatory T cells
What does cancer immunotherapy aim to do?
Give anti tumour effectors like T cells and antibodies to patients
Immunise patients against tumours
Stimulate patient’s own anti-tumour responses
What is passive immunotherapy?
It is passive immunity by transferring autologous (cells or tissues obtained from the same individual) T cells or monoclonal antibodies to kill the tumour.
How does antibody therapy work in killing tumour cells?
Monoclonal antibodies specific for tumour antigens activate effector mechanisms (like phagocytes, complement)
How does cellular therapy help in killing tumour cells?
Tumour-specific T cells from the patient are expanded in culture and injected back in
What is immune checkpoint blockade?
Tumour patients often mount ineffective T cell responses to tumours because of the upregulation of inhibitory receptors eg CTLA-4, and PD-1 on tumour-specific T cells
Expression of ligands like PD-L1 on tumour cells
The major cancer immunotherapy strategy in current practice is to release the inhibition by blocking molecules with monoclonal antibody (mAb) treatment:
anti-CTLA4 mAbs
block CTLA-4 on responding T cells or on Tregs
anti-PD-1 or anti-PD-L1 mAbs
Highly successful in treating patients with advanced cancers – BUT
> 50% do not respond & many develop autoimmune side effects
What are CAR T cells, and what are they used for:
Chimeric antigen receptor (CAR) T cells are genetically engineered patient T cells that recognise unprocessed antigens on the surface of tumour cells, without antigen presentation through MHC - allowing the direct killing
Chimeric antigen receptor: consists of an extracellular Ig domain that recognises a surface antigen on tumour cells and intracellular signalling domains from the TCR complex and costimulatory receptors that provide signals that activate the killing function of the T cells.
Has been successful in treating B-cell–derived leukaemia and lymphomas
