L14 - Cancer immunology

Question 1

What type of lymphocytes do many human cancers contain?

Answer 1

tumour infiltrating lymphocytes (TILs)

Question 2

If tumours are self tissue, how are they detected?

Answer 2

Tumour associated antigens (TAAs)

Question 3

Types of TAAs?

Answer 3

proteins escaping T-cell tolerance mechanisms: CTag, differentiation antigens, oncofoetal antigens

Neoantigens

other cancer specific alterations in proteins

Question 4

What are CTag?

Answer 4

found in developing testes

MAGE family molecules

Question 5

What are Differentiation antigens?

Answer 5

expressed at low level in normal development

greatly increased in tumour cells

Question 6

What are Oncofoetal antigens?

Answer 6

expressed during embryonic development before T cell development

Question 7

What are Neoantigens?

Answer 7

derived from mutated genes in cancer

e.g. p53 mutations

Question 8

What are other cancer-specific alterations in proteins?

Answer 8

changes in post-trans mods

aberrant splicing products

Question 9

Can you have an Ab response without T cells?

Answer 9

It is very difficult

Question 10

What are 3 E’s of cancer immunoediting?

Answer 10

1. Elimination
2. Equilibrium
3. Escape

Question 11

What happens in the elimination phase of cancer?

Answer 11

When tumours arise in tissue - immune cells can recognise and eliminate

Question 12

What happens in the equilibrium phase of cancer?

Answer 12

tumour cells arise more resistant

variety of tumour variants develop

Question 13

What happens in escape phase of cancer?

Answer 13

one variant may escape killing mechanism - or recruit regulatory cells to protect it = spread

Question 14

How can tumours evade T cells?

Answer 14

T cells can only see antigen in context MHC class I

without MHC class I - T cells are useless

Question 15

How can a cell lacking MHC class I be spotted?

Answer 15

NK cells destroy self-cells lacks MHC class I

Question 16

What are the inhibitory receptors that NK cells have for MHC class I?

Answer 16

Kiler inhibitory receptors (KIRs)

Question 17

WHat is the balance of signals for NK cells?

Answer 17

KIR (neg) and NKG2D (pos - activating receptor)

Question 18

What happens to ligands when MHC class I is lost?

Answer 18

E2F transcription factors - drive cell cycle AND expression of ligands of NKG2D

Question 19

What mechanisms do tumours use to evade immunity?

Answer 19

Loss of MHC class I

Loss of activating ligands (NKG2D)

Secretion of inhibitory metabolites

Apoptosis of immune cells

Initiation of immune checkpoints

Question 20

What 3 things happen when a T cell recognised a virus-infected cell via MHC class I and T cell receptor?

Answer 20

T cell kills infected cell

T cell makes pro-inflammatory cytokines

T cell expresses immune checkpoint molecules (PD-1) that inhibit T cell and self-limit immune response

Question 21

Mode of action of the PD-1 immune checkpoint?

Answer 21

T cell encounters tumour

activated - kills tumour

release IFN-y

upregulates PD-1

moves to next cell

T cell now inhibited via PD-1-PDL1 interaction

Question 22

What is PD-L1 on tumour cells induced by?

Answer 22

oncogene activity

IFN-y (from T-cells)

Question 23

Ligand of PD-1?

Answer 23

PD-L1

Question 24

3 types of immunotherapy for cancer?

Answer 24

Antibody targeting of tumour cells

T cell targeting of tumour cells

Inhibiting immune checkpoints with antibodies

Question 25

How does antibody-based targeting of tumour cells work as an immunotherapy?

Answer 25

REDIRECTS IMMUNITY TO THE TUMOUR CELLS

NK cells - Fc receptors, ADCC when recognise clustered IgG

complement-mediated destruction of B cell - CMC

cross linking of CD20 induces apoptosis

Question 26

name of antibody-based targeting of tumour cells immunotherapeutic agent?

Answer 26

Rituximab (chimaeric)

Question 27

How is T cell activity retargeted using CAR T cells?

Answer 27

replace T cell receptor with different antigen receptor based on an scFv antibody (fragment of variable region)

joined by linker - join to transmembrane and signalling domain that can act in T cells

Question 28

What are CAR T cells?

Answer 28

Chimeric Antigen Receptor T cells

Question 29

Problems with CAR T cells?

Answer 29

logisitics
cost
toxicity

Question 30

What is ICB (Immune checkpoint blockade) cancer treatment?

Answer 30

add antibody against PD-L1 to break inhibitor action

stops T cells receiving neg signals

now only get pos signals - enable attack of tumour cells