The role of the immune system in cancer

The immune system has a role in cancer (surprise!) Can be thought of having a role before AND after cancer Chronic inflammation can cause cancer The immune system can kill cancerous cells

Chronic inflammation and oncogenesis

It appears chronic inflammation can cause cancer 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 Therefore, anti-inflammatory cytokines or chemokines may be used to prevent cancer. NSAIDs have some effect for protecting against cancer

Immune response AGAINST cancer

How is the immune system protective against cancer? Destroys the infectious agent which can cause cancer Kills any cancerous cells before becoming a tumour Recap: innate immune response vs acquired immune response Innate immune response is the first-line protection mechanisms 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 Acquired immune response is the killing blow 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 Self-reactive cells are killed off during thymic selection to protect the body against auto-immune reactions The requirement of a danger signal will also prevent any self-reactive cells from being activated as well So How does that help against cancer? 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 What kind of immune response?
Oncology Page 1

 What kind of immune response? 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) Don't we have to worry about auto-immune reactions? 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 mutated proteins 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. If cells are kept in anergy, how do we activate them against cancer? 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 system will respond to necrosis with inflammation. So our immune system should work against cancer effectively right? Maybe but cancers can have immune defences Tumours will be subject to natural selection, because vulnerable cancerous cells will be killed off easily, leaving cells which are resistant to immune attack Plus they are more likely to be subject to mutations due to inactivated suppressor genes. 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 Or the person just can't mount a response Immunosuppressed due to drugs, infectious agents or radiation Plus as people get older, their immune system strength decreases Or the person produces the wrong 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) is to kill off these immunosuppressive cells and let the immune system clean up What if the cell stops producing MHC-I? 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.

Oncology Page 2