Cancer Immunology

The great escape artist -the cancer cell

Have you ever wondered how cells become cancer? Most of our cells contain DNA (deoxyribonucleic acid) that consist of genes. Genes provide instructions to build proteins such as antibodies. These built proteins are copied and multiplied.

If we lived in a perfect world then these protein copies would be identical but since we don’t live in a bubble, perfection fails. Our bodies are exposed daily to insults that cause damage to our cells. These insults could be from a poor diet ingested, environmental exposure or infections that damage or mutate cells. It is not unusual for our cells to experience tens of thousands of insults per day. Our immune system is constantly monitoring for damaged and mutated cells and thankfully kills cancer cells on a daily basis. We can thank both T cells and Natural Killer Cells (NKC) for identifying mutated cells and killing them before they can grow large enough to be discovered during health exams.

The immune system can deal with damaged cells as long as it can recognize the abnormalities. However, the damaged cells cleverly hide from the immune system. The real danger happens when the clever cells multiply quickly and overburden the immune system. At this point the number of mutated cells outmatch our immune cells who then become exhausted and lose the battle. This is when cancer or autoimmune diseases develop. Once the damaged cell has the upper hand it continues to mutate and fight the immune system. Cancer cells are multi-talented and can not only hide but also produce molecules that create an environment that is hostile for the immune cells, rendering those powerful NKC inactive.

We also have genes that help us from developing cancer. Tumor suppressor genes are able to stop the excessive copying, repair the damaged DNA or induce apoptosis (cell death). Some people are born with mutations to some of these tumor suppressors and they do not work as well which can increase the multiplication of damaged cells that lead to cancer. We also have genes called proto-oncogenes that help control cell division. When these cells mutate, they become oncogenes and lose that ability to protect us.

DNA is structured with nucleotides that are familiar to most people as the double helix strands that contain base pairs Adenine (A) & Guanine (G) Cytosine (C) & Thymine (T) linked together in a very specific order. In the perfect world these base pairs would copy as instructed but with the daily insults we receive the base pairs can get mixed up such as A taking the position of a C. When this happens, we call this a SNP (single nucleotide polymorphism).

When we get our DNA tested and the results tell us that we are at risk for certain diseases including specific types of cancers, this is a result of SNPs we are born with. Just because we have the SNP does not guarantee you will get said cancer. The risk of cancer increases when the gene is turned on by one of those many insults we receive in life. Examples could be getting a virus or infection that increases inflammation and turning on that gene. Combinations of SNPs are also more important than a single SNP in predicting cancer risk.

Certain situations or conditions will compromise our immune system. Aging is the number one risk factor for developing cancer. Reasons for this include decreased immune function as we age. Each type of immune cell is affected by age in unique ways:

• dendrite cells become less able to uptake antigens or signal T cells to the site of damage

• neutrophils become less effective at neutralizing bacteria

• macrophages consume less damaged cells allowing those clever cells to multiply

Many of these innate immune changes slow down the initiation of adaptive immune response as well. Speaking for our adaptive immune aged response, T cells begin to have replication stress which increases gene mutations. This abnormal replication leads to T cell exhaustion. T regulatory cells are a bit stronger and have selective dysregulation, but they begin to be less efficient at fighting cancer.

Summary Points

• Daily damage occurs to our cells. Damage occurs from environmental exposures such as UV sunlight on our skin, the polluted air we breathe or a nutrient sparse diet.

• Our immune system monitors our cells constantly - cleaning up the damage and fights cancer daily.

• The cancer cell is very smart and develops unique ways to escape the immune system.

• Cancer happens when our immune cells are overburdened by too much inflammation and damage and get exhausted and it can become a losing battle with cancer cells winning.

References

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