Tumour Immunology + Other Hallmarks of Cancer Flashcards
How are cancer cells sometimes recognised as non-self?
Hallmark of cancer = mutations
- > change in proteins
- > peptides displayed on plasma membrane (act as antigen)
- > which are recognised as non-self
What are the stem cell precursors called in haematopoiesis?
Haematopoietic stem cell
What are the 2 distinct lineages formed in haematopoiesis?
Myeloid
Lymphoid
Where do a lot of immune response occur?
Lymphatic system
What type of immunity involves antibodies? What cells are involved?
Humoral (adaptive) immunity
B-cells
What does adaptive mean?
Immune cells are taught to attack previously encountered antigens on a cell
What does innate mean?
Immune cells recognise new non-self cell surface proteins
What are the 2 types of cellular immunity?
Specific (adaptive)
Nonspecific (innate)
What cells are involved in specific cellular immunity?
T-cells
= Cytotoxic T-cells
= Helper T-cells
= Regulatory T-cells
What do regulatory T-cells do?
In specific cellular response
Inhibit cytotoxic + helper T-cells
What do cytotoxic T-cells do?
Kills target cells
What do help T-cells do?
In specific cellular response
Stimulate cytotoxic T-cells + proliferation of plasma cells (-> increase antibody production)
What is MHC?
Major histocompatibility complex
= cell surface proteins
What type of cells express MHC class I?
Almost all cell types including cancer cells
What type of cell express MHC class II?
Professional immunocytes
= antigen-presenting cells
= e.g. phagocytes
What cell can interact w/ MHC? What part specifically is bound to MHC?
T-cells
T-cell receptors (TCRs)
What is the costimulating molecules for MHC class I?
CD8
What is the costimulating molecules for mHC class II?
CD4
CD8 + CD4 are expressed by which cells?
T-cells
Describe the “war” between cancer + the immune system through cancer progression
Early stages of cancer progression (in situ tumour/premalignant lesion):
= Immune system = highly active
= Typically destroys majority of cancer cells
= Cancer cells recognise as non-self
= Don’t eliminate all cancer cells
Equilibrium:
= Not all cancer cells are targeted
= Dampening of immune system
-> tumour grows
Later stages of cancer progression:
= Mutations allows cancer cells to escape detection by immune system
= Mutations that dampens immune system
-> Tumour grows
What do cancer cells express that binds w/ MHC I?
Tumour-associated antigen (TAAs)
Describe the 2 mechanisms of how cytotoxic T-cells cause apoptosis in cancer cells
1) Cytotoxic T-cells perforate surface of cancer cells (perforin makes channels)
= Releases granzymes to cancer cells
= Granzymes activate caspases inside -> apoptosis
2) Active induction of apoptosis
= Mediated by cytotoxic T-cells
= Release death ligands which bind to death cell receptors on cancer cells
Name the 2 molecules involved in the immune checkpoint
PDL1
CTLA-4
How can cancer cells avoid immune system (immunoevasion)?
Hide from Tc (by repressing expression of MHC/tumour antigens)
Hide stress from NK cells (by repressing expression of stress proteins)
Inactivate immunocytes (Tc + NK) (by secreting immunosuppressive proteins e.g. TGF-beta/IL-10)
Induce Tc apoptosis (by releasing apoptotic/death ligands e.g. FasL)
Develop resistance to FasL mediated apoptosis
Attract other Treg cells that inhibit Tcs
What is over expressed in cancer cells that results in weight loss?
Glucose transporters
Glucose in cancer cells usually enter what metabolic pathway?
What are the possible reasons for this?
Anaerobic/lactate/glycolytic
To make building blocks to make more cells -> proliferation
OR
Avoid mito. as it secretes cyto. c which induces apoptosis
What are the cells suggested to be the derivation of leukaemia stem cells?
Haematopoietic stem cells
Immature mutant haematopoietic progenitors
