Tumour Immunology

Question 1

What is a hallmark of cancer?

Answer 1

The ability to evade immune destruction

Question 2

What is immune surveillance?

Answer 2

A constant control and elimination of malignant cells by the immune system

Question 3

How do normal cells become tumour cells?

Answer 3

In response to oncogenic stimuli (carcinogens, radiation etc) they transform into tumour cells

Question 4

How is the cancer immunoediting process initiated?

Answer 4

The tumour cells’ expression of tumour specific markers and proinflammatory danger signals

Question 5

What is cancer immunoediting?

Answer 5

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

Question 6

What is evidence for immune responses against tumour growth, that inhibit the tumour?

Answer 6

Lymphocytic infiltrates around some tumours
Enlargement of draining lymph nodes

= better prognosis

Question 7

Evidence that the immune system protects against tumour growth

Answer 7

Immunodeficient individuals have an increased incidence of some types of tumours

Question 8

Evidence for the fact that tumours evade immune surveillance by engaging inhibitory receptors on T cells

Answer 8

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

Question 9

What is the principal mechanism of tumour eradication?

Answer 9

Killing by cytotoxic T cells, specific for the tumour antigen

Question 10

How are CTL responses induced?

Answer 10

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

Question 11

Are NK cells capable of killing tumour cells? If so, how?

Answer 11

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)

Question 12

CD4+ anti tumour responses

Answer 12

Increased numbers of Th1 cells in the tumour infiltrates are associated with a good prognosis

Th1 cells work by activating macrophages

Question 13

Are anti-tumour antibodies detectable in some cancer patients?

Answer 13

Yes

Question 14

How and why are immune responses against tumours weak?

Answer 14

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

Question 15

What does cancer immunotherapy aim to do?

Answer 15

Give anti tumour effectors like T cells and antibodies to patients

Immunise patients against tumours

Stimulate patient’s own anti-tumour responses

Question 16

What is passive immunotherapy?

Answer 16

It is passive immunity by transferring autologous (cells or tissues obtained from the same individual) T cells or monoclonal antibodies to kill the tumour.

Question 17

How does antibody therapy work in killing tumour cells?

Answer 17

Monoclonal antibodies specific for tumour antigens activate effector mechanisms (like phagocytes, complement)​

Question 18

How does cellular therapy help in killing tumour cells?

Answer 18

Tumour-specific T cells from the patient are expanded in culture and injected back in​

Question 19

What is immune checkpoint blockade?

Answer 19

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​

Question 20

What are CAR T cells, and what are they used for:

Answer 20

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