8/2/2019 The Role of the Immune System in Cancer

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Chronic inflammation can cause cancer○

The immune system can kill cancerous cells○

Can be thought of having a role before AND after cancer•

The immune system has a role in cancer (surprise!)

Chronic inflammation and oncogenesis

Inflammation produces some reactive oxygen species which may damage

DNA, causing activation/inactivation of genes

○

Inflammation also encourages division of some cells (especially immune

cells) which can lead to cancer

○

It appears chronic inflammation can cause cancer•

NSAIDs have some effect for protecting against cancer○

Therefore, anti-inflammatory cytokines or chemokines may be used to prevent

cancer.

•

Immune response AGAINST cancer

Destroys the infectious agent which can cause cancer○

Kills any cancerous cells before becoming a tumour○

How is the immune system protective against cancer?•

Neutrophils, macrophages and dendritic cells

Detect foreign cells, and abnormal body cells (due to infection or

cancer) to trigger an immune response (produce cytokines and stuff),especially trigger the acquired immune response

Slow down the infection long enough for the acquired immune

system to kick in

Innate immune response is the first-line protection mechanisms○

T Lymphocytes for a cellular immune response, B lymphocytes for a

humoural (antibody) response

Produces more effective killing cells (natural selection, where

lymphocytes with the best receptor against the antigen is stimulated

more)

Produces memory cells to prevent long term recurrence

Acquired immune response is the killing blow○

The requirement of a danger signal will also prevent any self-reactive

cells from being activated as well

Self-reactive cells are killed off during thymic selection to protect the bodyagainst auto-immune reactions

○

Recap: innate immune response vs acquired immune response•

•

All nucleated cells are able to get cancerous○

But all nucleated cells must express MHC-I○

The MHC-I is continuously recycled from displaying an antigen and being

drawn back into the cell to find a new antigen to display

○

Normally, the immune cells will see all the MHC-I receptors displaying

normal body antigens

○

But if the cell becomes cancerous, it will start producing antigens the

immune system can't recognise

○

This will lead to an immune response○

So… How does that help against cancer?

 

The role of the immune system in cancer

Oncology Page 1

8/2/2019 The Role of the Immune System in Cancer

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•

Because it's MHC-I, it needs CD-8 co-receptor to stimulate CD8 T cytotoxic

cells

○

Therefore, the immune response will be mainly carried out by CD8 T

lymphocytes (cellular response)

○

What kind of immune response?

•

Well, it's not the same as the diseases we've seen in the past○

Tumours will make 'Tumour specific antigens' (TSA) which are the mutatedproteins the immune system can't recognise

○

In addition, they might also make 'Tumour associated antigens' (TAA) ,

which is where the tumour produces proteins which shouldn't belong in

that part of the body

○

Lastly, an infectious agent can be causing cancer, these cells will display

viral antigens to become a target for the immune system as well.

○

Don't we have to worry about auto-immune reactions?

•

○ Danger signals can come from infected cells at least

○ Also, if a tumour does form, then the centre of the tumour may become

necrotic due to reduced blood supply to the region. The immune systemwill respond to necrosis with inflammation.

If cells are kept in anergy, how do we activate them against cancer?

•

□ Plus they are more likely to be subject to mutations due to

inactivated suppressor genes.

Tumours will be subject to natural selection, because vulnerable

cancerous cells will be killed off easily, leaving cells which are

resistant to immune attack

They can look normal to the immune system by expressing normal

antigens on MHC-I They can shut down antigen presentation (however, see below)

They can produce an environment which can be immunosuppressive

○ Maybe… but cancers can have immune defences

Immunosuppressed due to drugs, infectious agents or radiation

Plus as people get older, their immune system strength decreases

○ Or the person just can't mount a response

The immune system decides to induce tolerance against the tumour

cells, preventing any immune cells from attacking it

Or… the tumour cell or supporting cells will produce

immunosuppressive factors like cytokines

So one important result of treatment (radiation, chemo or surgery) isto kill off these immunosuppressive cells and let the immune system

clean up

○ Or the person produces the wrong response

So our immune system should work against cancer effectively right?

○ It's one method to prevent the immune system from noticing

○ But Natural Killer (NK) cells will be able to detect if a cell is missing MHC-I

○ NK cells are always set to kill, so they need an inhibitory signal to prevent

the cell from being killed

○ MHC-I provides the inhibitor signal, so cells with MHC-I will survive

○ Cells which do not produce display MHC-I cannot send the inhibitory signal,

and so they will die.

• What if the cell stops producing MHC-I?

Oncology Page 2