The Immune System:
“Catch Me If You Can”

It was not always clear to scientists that the immune system played a role in preventing and combating cancer. This idea was proposed in 1957, but the scientific evidence at the time only seemed to indicate that the immune system protected against pathogens like viruses and bacteria, but not against abnormal body cells like cancer cells.

Researchers and doctors in the late 1900s noticed, however, that people with extremely weak or nonexistent immune systems had a greater risk of developing cancer than the average person. In addition, researchers have since noticed that patients with immune cells present in their tumors have a better prognosis than patients without immune cells in their tumors.

The immune system is a network of cells, tissues, and organs that work together to defend the body against attacks by "foreign" invaders.

Image courtesy of the National Cancer Institute

These are primarily microbes (tiny infectioncausing organisms such as bacteria, viruses, parasites and fungi); however researchers now know that cancer cells also must evade the immune system.

You can think of the immune system as a small army that is always waiting to defend your body against invasion.

The key to a healthy immune system is its remarkable ability to distinguish between the body's own cells, recognized as "self," and foreign cells, or "nonself." The body's immune defenses normally coexist peacefully with cells that carry distinctive "self" marker molecules. But when immune defenders encounter foreign cells or organisms carrying markers that say "nonself," they quickly launch an attack.

 

How The Immune System Works:

"The immune system is composed of three "layers" or mechanisms that protect humans from disease.

• The first line of defense, the skin and mucous membranes, acts as a physical barrier.
• The second layer is the innate immune system, a broad-acting, short-term, nonspecific immune response to pathogens such as bacteria or viruses.
• Microbes that evade the innate system encounter a third layer of protection; a second, more powerful immune mechanism called the adaptive immune response. Through adaptive immunity, populations of white blood cells known as lymphocytes - B cells and T cells - mount a powerful, highly specific immune system attack on specific pathogens."

This section excerpted from Bio-Medicine

Antigens:

Anything that can trigger an immune response is called an antigen. An antigen can be a microbe such as a virus, or even a part of a microbe. Tissues or cells from another person (except an identical twin) also carries nonself markers and act as antigens. This explains why tissue transplants may be rejected.

The antigens expressed by tumors have several sources:

• Some are derived from oncogenic viruses
  • For example, human papillomavirus, which causes cervical cancer
• Others are the organism's own proteins that occur at low levels in normal cells but reach high levels in tumor cells.
  • One example is an enzyme called tyrosinase that, when expressed at high levels, transforms certain skin cells (e.g. melanocytes) into tumors called melanomas.
• A third possible source of tumor antigens are proteins normally important for regulating cell growth and survival that commonly mutate into cancer, inducing molecules called oncogenes.

 

How the Immune System Identifies and Eliminates Tumors:

The main response of the immune system to tumors is to destroy the abnormal cells using killer T cells, sometimes with the assistance of helper T cells. Clearly, some tumors evade the immune system and go on to become cancers.

		Tumor cells often have a reduced number of specialized molecules on their surface, thus avoiding detection by killer T cells. Some tumor cells also release products that inhibit the immune response, for example, by secreting the cytokine TGF-ß, which suppresses the activity of macrophages and lymphocytes. In addition, immunological tolerance may develop against tumor antigens, so the immune system no longer attacks the tumor cells.
Image courtesy of the National Cancer Institute

Many cancers (gastric, cervical, colon, liver) are associated with infection and correlate with the activity of the normal host immune response. Chronic inflammatory conditions make people more likely to develop certain cancers; for example, patients with Crohn's disease have a higher incidence of colorectal cancer.

A greater understanding of the ways by which the inflammatory response initiates cancer may lead to potent new cancer treatments.

Immunosurveillance

This is a term used to describe the action of the immune cells, including T cells, as they move through the body and look for any abnormalities. When cells become mutated, they may appear to the immune cells as abnormal. The body then recognizes them as non-self or foreign.

By eliminating cells that have become abnormal, the immune system helps to protect against cancer. However, if the cells mutate enough so that they are able to escape the surveillance mechanisms of the immune system, they may continue to reproduce as cancer cells. The process is a complex version of 'hide and seek' with major consequences.

The secret to its success is an elaborate and dynamic communications network. Millions and millions of cells, organized into sets and subsets, gather like clouds of bees swarming around a hive and pass information back and forth in response to an infection.

Immunotherapy and cancer vaccines

Attempts to provide the immune system with the signals that it needs to recognize the cancer cells as abnormal. If successful, these strategies may allow the body to recognize and destroy cancer cells, even those that have been able to form a tumor.

		The image depicts manufactured antibodies zeroing in on a large cancer cell. The antibodies will attach to antigens on the cancer cell and dispense a drug to kill it.
Image provided by CISN archives. All rights reserved.

 

CISN Summary

At every level in its life, a cancer cell and its daughter clones must evade the immune system. The immune system is a remarkably adaptable system that seeks out and destroys foreign and harmful agents within an organism.

Cancer cells have developed several ways to evade the surveillance of the immune system. Many cells have lost proteins (antigens) on their cell surface so that the body can't recognize that these cells are foreign. Other cancer cells secrete cytokines such as transforming growth factor beta (TGFß), which inhibit the function of the immune system.

• Cancer cells send signals to the immune system that, in turn, support or suppress tumor development.
• In particular, macrophages (a type of white blood cell that surrounds and kills microorganisms), removes dead cells, and stimulates the action of other immune system cells, seem to play an important role in cancer.