Tumour Immunology + Other Hallmarks of Cancer

Question 1

How are cancer cells sometimes recognised as non-self?

Answer 1

Hallmark of cancer = mutations

• > change in proteins
• > peptides displayed on plasma membrane (act as antigen)
• > which are recognised as non-self

Question 2

What are the stem cell precursors called in haematopoiesis?

Answer 2

Haematopoietic stem cell

Question 3

What are the 2 distinct lineages formed in haematopoiesis?

Answer 3

Myeloid

Lymphoid

Question 4

Where do a lot of immune response occur?

Answer 4

Lymphatic system

Question 5

What type of immunity involves antibodies? What cells are involved?

Answer 5

Humoral (adaptive) immunity

B-cells

Question 6

What does adaptive mean?

Answer 6

Immune cells are taught to attack previously encountered antigens on a cell

Question 7

What does innate mean?

Answer 7

Immune cells recognise new non-self cell surface proteins

Question 8

What are the 2 types of cellular immunity?

Answer 8

Specific (adaptive)

Nonspecific (innate)

Question 9

What cells are involved in specific cellular immunity?

Answer 9

T-cells
= Cytotoxic T-cells
= Helper T-cells
= Regulatory T-cells

Question 10

What do regulatory T-cells do?

Answer 10

In specific cellular response

Inhibit cytotoxic + helper T-cells

Question 11

What do cytotoxic T-cells do?

Answer 11

Kills target cells

Question 12

What do help T-cells do?

Answer 12

In specific cellular response

Stimulate cytotoxic T-cells + proliferation of plasma cells (-> increase antibody production)

Question 13

What is MHC?

Answer 13

Major histocompatibility complex

= cell surface proteins

Question 14

What type of cells express MHC class I?

Answer 14

Almost all cell types including cancer cells

Question 15

What type of cell express MHC class II?

Answer 15

Professional immunocytes
= antigen-presenting cells
= e.g. phagocytes

Question 16

What cell can interact w/ MHC? What part specifically is bound to MHC?

Answer 16

T-cells

T-cell receptors (TCRs)

Question 17

What is the costimulating molecules for MHC class I?

Answer 17

CD8

Question 18

What is the costimulating molecules for mHC class II?

Answer 18

CD4

Question 19

CD8 + CD4 are expressed by which cells?

Answer 19

T-cells

Question 20

Describe the “war” between cancer + the immune system through cancer progression

Answer 20

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

Question 21

What do cancer cells express that binds w/ MHC I?

Answer 21

Tumour-associated antigen (TAAs)

Question 22

Describe the 2 mechanisms of how cytotoxic T-cells cause apoptosis in cancer cells

Answer 22

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

Question 23

Name the 2 molecules involved in the immune checkpoint

Answer 23

PDL1

CTLA-4

Question 24

How can cancer cells avoid immune system (immunoevasion)?

Answer 24

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

Question 25

What is over expressed in cancer cells that results in weight loss?

Answer 25

Glucose transporters

Question 26

Glucose in cancer cells usually enter what metabolic pathway?
What are the possible reasons for this?

Answer 26

Anaerobic/lactate/glycolytic

To make building blocks to make more cells -> proliferation
OR
Avoid mito. as it secretes cyto. c which induces apoptosis

Question 27

What are the cells suggested to be the derivation of leukaemia stem cells?

Answer 27

Haematopoietic stem cells

Immature mutant haematopoietic progenitors