Cancer and immune system

ByNida Sajjad

Mphil Zoology University of Sargodha

Contents• Introduction• What is immune system?• What is cancer?• How cancer weakens immune

system?• Cancer and parts of immune system• Tumor antigens• Immunoediting• Treatment of cancer and elements of

immune system• Conclusion

What the immune system does

• It protects the body against illness and infection caused by bacteria, viruses, fungi or parasites and transformed cells.• It is a collection of reactions and responses that

the body makes to damaged cells or infection. So it is sometimes called the immune response.

What is cancer?

How immune system is important to cancer patients?

• It is important to cancer patients in many ways because it is two- way fight

Cancer and cancer treatments can weaken the immune system.

The immune system may help to fight cancer

How Cancer and its treatments may weaken immunity

• It can weaken the immune system by Spreading into bone marrow.Cancer in the bone marrow stops it making so many blood cells.

• Weakening of the immune system happens in leukaemia or lymphoma. But it can happen with other cancers too.

• Chemotherapy, biological therapies and radiotherapy can temporarily weaken immunity by causing a drop in the number of white blood cells made in the bone marrow.

Immune system can help to fight cancer

• Some cells (CD8 killer cells) of the immune system can recognise cancer cells as abnormal and kill them.

• Unfortunately, it is not enough to get rid of a cancer.But some new treatments aim to use the immune

system to fight cancer.

• As there are two parts of immune system

The inbuilt protection from birth (innate)

The immune protection developed from being exposed to certain diseases (acquired)

In built immune protection(innate immunity)

• Always ready and prepared to defend the body against foreign attack. • It involves skin as anatomical barrier, inner

linings of the gut and lungs, which produce mucus and trap invading bacteria as physiological barrier.• Stomach acid which kill bacteria and urine

flow, which flushes bacteria out of the bladder and urethra.WBCs which kill bacteria.

How these natural mechanisms disturbed if you have cancer?

• Chemotherapy may damage to the lining of the gut – e.g,severe diarrhoea caused by some chemotherapy drugs can break down the gut lining.

• A catheter into your bladder can become a route for bacteria to get inside the bladder and cause infection.

• Radiotherapy to the lung can damage the hairs and mucus producing cells that help to remove bacteria.

• Anti acid medicines for heartburn may neutralise the stomach acid that kills bacteria.

• Chemotherapy can temporarily reduce neutrophil in the blood which means it is more difficult to fight off infection.

Acquired immune system and cancerous cells

• Cancer cells are not normal cells. So some antibodies produced by B cells with variable ends recognise cancer cells and stick to them.

• Killer T cells (CD8+ T cells) kill the body's own cells that have been transformed.

Tumor antigens• Two types of tumor antigens have been identified on tumor cells.Tumor-specific Transplantation Antigens(TSTAS) Tumor-associated Transplantation Antigens(TATAS)• TSTAs are unique to tumor cells and do not found on normal cells.• They result from mutations in tumor cells that generate altered cellular proteins.• Cytosolic processing of these proteins would give rise to new peptides that are

presented with class I MHC molecules.• These induce a cell-mediated response by tumor-specific CTLs(Cytotoxic T

lymphocytes)

Tumor Associated Antigens• TATAs which are not unique to tumor cells are expressed on normal

cells during fetal development when the immune system is immature and unable to respond but that are not expressed in the adult.

• Reactivation of the embryonic genes that encode these proteins in tumor cells results in their expression on the fully differentiated tumor cells.

• Tumor-associated antigens are normally expressed at extremely low levels on normal cells but are expressed at much higher levels on tumor cells

Immunoediting• Immunoediting is a process by which a person is

protected from cancer growth and the development of tumor immunogenicity by their immune system.

• PhasesEliminationEquilibrium Escape

Elimination Phases

• It has following four phases• Elimination: Phase 1• The first phase of elimination involves the initiation of an antitumor

immune response.• It involves recognition of growing tumor causing local tissue damage.• As a result inflammatory signals are produced which help in recruitment of

innate immune cells (natural killer cells, natural killer T cells, macrophages and dendritic cells) to the tumor site.

• During this phase, the infiltrating lymphocytes such as the natural killer cells and natural killer T cells are stimulated to produce IFN-gamma.

Elimination: Phase 2

• In this phase,newly synthesized IFN-gamma induces tumor death and promote the production of chemokines( CXCL10, CXCL9and CXCL11).

• These chemokines block the formation of new blood vessels.

• Tumor cell debris produced as a result of tumor death is ingested by dendritic cells, followed by the migration of these dendritic cells to the draining lymph nodes.

Elimination: Phase 3• NK cells and macrophages transactivate(crosstalk of

signaling cascade) one another by reciprocal production of IFN-gamma and IL-12. This results in more tumor killing by these cells via apoptosis and the production of reactive oxygen and nitrogen intermediates.

• In the draining lymph nodes, tumor-specific dendritic cells trigger the differentiation of Th1 cells which in turn facilitates the development of CD8+ T.

Elimination: Phase 4• In the final phase, tumor-specific CD4+ and CD8+ T cells home to the

tumor site and the cytolytic T lymphocytes then destroy the antigen-bearing tumor cells which remain at the site.

• Equilibrium phase:• Those tumor cell which have survived the elimination phase enter the

equilibrium phase.• In this phase, lymphocytes and IFN-gamma exert a selection pressure on

tumor cells which are genetically unstable and rapidly mutating. • Escape phase:• Tumor cell which have acquired resistance to equilibrium phase then enter

the escape phase. Where tumor cells continue to grow and expand in an uncontrolled manner and eventually lead to malignancies.

Cancer treatments that use the immune system

• Some cancer treatments use elements of the immune system to help treat cancer.

• ImmunotherapyImmunotherapy is a type of biological therapy.  It uses natural body substances or drugs made from these substances to treat cancer. 

• Interferon alpha and IL-2 act by boosting the immune response to help the body kill off cancer cells.

Monoclonal antibodies

• Monoclonal antibodies are made in the laboratory and they have same variable end.• These antibodies recognise molecules on the outside of cancer cells.• Different antibodies have to be made for different types of cancer.As Rituximab (Mabthera) recognises CD20 protein on the outside of some

lymphoma cells.Bevacizumab (Avastin) targets growth factors that help blood vessels grow and is

used to treat bowel cancer, breast cancer and some other types.Trastuzumab (Herceptin) recognises breast cancer cells that produce too much

of the protein HER 2(human epidermal growth factor receptor 2).This protein can make breast cancer more aggressive.

Manipulation of Co-Stimulatory Signals Can Enhance Immunity

• Tumor immunity can be enhanced by providing the co-stimulatory signal necessary for activation of CTL precursors (CTL-Ps).

Cancer Treatment Vaccines• Use of therapeutic vaccines is another approach to immunotherapy. • These vaccines are made from a patient’s own tumor cells or substances from

tumor cells. • They are designed to strengthen the body’s natural defenses against the cancer.• Treatment vaccines may act in any of several ways:• to delay or stop the growth of cancer cells• to cause tumor shrinkage• to prevent cancer from coming back• to eliminate cancer cells that have not been killed by other forms of treatment

Conclusion

• Cancer can weaken immune system by distrupting different types of barriers of immune system but individual having strong immune system can cope with abnormality to best possible limit.