Cancer and the Immune System Flashcards
What are the most abundant stromal cells that surround tumour cells?
Vascular network Fibroblasts Immune cells
Stromal cells
Stromal cells are connective tissue cells of any organ
- they support the parenchymal cells of that organ.
How do stromal cells affect tumour development?
Stromal cells can both inhibit and promote tumour development.
- not stromal cells promote tumour growth more than they inhibit it.
What are the key pro-tumourigenic mechanisms?
Anti-apoptopic Pro survival Mitogenic Pro invasive
K-RAS mutations are implicated as being involved in what cancers?
Pancreatic and colorectal cancers.
Explain the role of tumour elicited inflammation in tumour development.
- Oncogene activation - leads to development of tumour cells.
- Tumour cells activate and secrete tumour-derived factors such as cytokines and chemokines.
- Cytokines and chemokines are inflammatory recruitment cells and recruit macrophages, dendritic cells and T/B cells.
- The immune cells then induce further the activation of cancer cells and secrete more chemokines and cytokines.
The destruction of cancer cells is mediated by what immune cells?
Cytotoxic T lymphocytes (CTLs; CD8+ T cells, effector cells).
How do CTL’s kill cancer cells?
The T cell receptor of the CTL (effector cell) interacts with the MHC Class I complex expressed on the cancer cell (target cell). This activates the CTL causing it to secrete perforin which is a granzyme that hydrolyses the cancer cell membrane.
How does the immune system recognise cancer cells?
CD8+ cells bind to MHC class 1 complexes on the tumour cells, with their T cell receptor.
What do major histocompatibility complexes do?
They present the proteins made by a cell on the cells surface enabling it’s identification.
Explain the steps of Cytotoxic T cell activation to destruction of the tumour cell.
- The CTL’s are activated in the lymph nodes when their receptor binds to an MHC.
- This stimulates CTL activation and maturation.
- The cytotoxic T cell then travels to the tumour site and destroy the tumour cells by release of perforins and granzymes.
The cancer immunity cycle - the steps needed for an anti-tumour response:
Regarding the role of immunity in cancer explain the the three E hypothesis.
Tumour elimination
Tumour equilibrium
Tumour growth (escape)
What are the tumour immune escape mechanisms?
- Immunosupressive cells
- Loss of tumour antigen expression
- Inhibition of T cell infiltration
- Inhibition of T cell activation
What are the main immunosuppressive cells in cancer?
Regulatory Tcell Tregs
Myeloid derived supressor cells
Alternative activated macrophages
What do immunosupressive cells do in cancer?
Immunosuppressive cells inhibit the activation and /or function of cytotoxic T cell (CTLs) in the tumour microenvironment. CTLs are no longer able to efficiently kill cancer cells.
What are the three mechanisms that can lead to loss of antigen presentation in cancer cells?
- Reduced expression of MHC Class I on cancer cells
- Inhibition of antigen processing in cancer cells.
- Loss of tumour antigen.
Can cells present which MHC class recognised by what cells of the immune system?
Cancer cells present MHC class 1 antigens on their cell surface which are recognised by CD8+ cells.
What are the two ways you can have inhibition of T cell infiltation?
(specifically CD8+)
- Inhibition of T cell extravasation: Abnormal tumour blood vessels express molecules which kill T cells during the extravasation step. (Examples: Endothelin, Fas – Ligand).
- Inhibition of T cell infiltration: Cancer cells induce the generation of an exessive fibrotic tumour microenvironment which acts as a physical barrier for T cells. (Examples: Fibrosis, desmoplasia).
Define extravasation regarding inflammation.
In the case of inflammation, it refers to the movement of white blood cells from the capillaries to the tissues surrounding them, also known as diapedesis.
What are the three different signals T cells need for their full activation?
T cells need three different signals for their full activation:
1st TCR: stimulate by epitope presented on MHC I
2nd Co-stimulatory molecule: stimulated by CD80 or CD86 ligation.
3rd activating cytokines.
How do tumour cells inhibit T cell activation?
Tumour cells cells hijack the inhibitory signalling pathways preventing T cell activation.
Occurs at the immune checkpoint receptors.
What are PD1 and CTLA4 examples of?
Inhibitory immune checkpoint receptors.
- inhibit T cell activation.
PD1
What is PD1’s relevance in cancer?
Programmed death cell protein
Cancer cells express the ligand for PD-1 (PD-L1) to inhibit activated T cells.
Anti-PD-1 antibodies block the ligation of the PD-1 receptor on the T cell and thus the T cells remains active.
