Cancer Immunotherapy

Harness and Unleash the Power of the Immune System

Your immune system is a powerful protection mechanism that works around the clock to defend you from harmful germs and internal stresses to normal cells in the body. After years of research, doctors have found a way to unleash its cancer-fighting potential, too. Immunotherapy harnesses the power of the immune system by helping it recognize cancer cells that have been hiding and targeting them for destruction. This guide explains how the immune system works, the various types of immunotherapy available and ways to help manage your treatment and follow-up care.

To understand how your immune system can be used to treat cancer, it’s helpful to know how it works. It’s a complex network of cells, molecules, organs and lymph tissues working together to defend the body against germs and other microscopic invaders from the environment. It can protect against cell damage or stress, and even fight cancer cells.

A significant benefit of the immune system is its ability to create immunity, or protection, from infectious disease (see How the Immune System Remembers, below). A major advantage is that once the immune system has been engaged in fighting an infection, it can remember and provide long-term, in some cases life-long, protection against a specific infection. And this advantage is key to using immunotherapy against cancer.

Immunity can be natural (innate) or acquired (adaptive). People are born with natural immunity, which includes physical barriers to the internal body parts and offers several defenses against harmful microorganisms. Barriers include skin and mucous membranes, which prevent harmful substances from entering the body. This protection is non-specific, meaning it does not target any particular harmful organism.

The acquired immune system is built up over time through exposure to germs in the environment. This provides protection against multiple types of infections, and this occurs because infectious organisms (or germs) have proteins called antigens, which are substances that stimulate an immune response. Antigens include toxins, chemicals, bacteria, viruses or other substances that originate outside the body. The acquired immune system can adapt to new germs and remember them, providing longer-lasting protection. This long-lasting protection is called immune memory.

Germs sometimes get past these defenses. When you scrape the palm of your hand, for example, the barrier is broken and harmful substances can easily enter the body (see Figure 1). Immediately after the injury, immune cells in the injured tissue begin to respond. They call other immune cells that have been circulating in your body to gather at the site where antigens are entering the body. The immune cells identify the antigens as dangerous and begin to destroy them with a general attack. This is called an immune response.

How the Immune System Works

The first job of the immune system is to distinguish between what is part of the body (self) and what is not part of the body (non-self or foreign). Viruses are one type of non-self germ that can infect humans as they enter, and often hide inside, the normal cells of the body.

The immune system has developed sophisticated ways to determine if a cell is normal or if it may contain a virus or be abnormal for other reasons, such as injury or cancer. The immune system recognizes abnormal cells or germs by “seeing” antigens, which are the specific proteins or other molecules on the surface of an infected or abnormal cell. Once the immune system determines that a cell is not normal (or foreign to the body), the immune system begins a series of reactions to identify, target and eliminate the abnormal cell.

The driving force of the immune system is the lymphatic system, which is made up of the spleen, thymus, adenoids, tonsils and lymph nodes. Lymph, a clear fluid, circulates throughout the lymphatic system and through the lymph nodes. It collects and filters bacteria, viruses, toxins and chemicals, which are circulating in the lymphatic system and bloodstream. Lymph nodes are small bean-shaped structures located throughout the body, with large concentrations near the chest, abdomen, groin, pelvis, underarms and neck.

Lymph contains lymphocytes, a type of white blood cell that attacks infectious agents and abnormal cells. The two main types of lymphocytes are B-lymphocytes (B-cells) and T-lymphocytes (T-cells).

B-cells develop in the bone marrow and mature into either plasma cells or memory cells. B-cells produce protein antibodies that attach to infectious organisms, such as bacteria and some viruses, marking them for destruction. However, they can only identify them, not destroy them. Plasma cells make antibodies to fight germs and infection. Memory cells help the body remember which antigens have been attacked previously so it can recognize them more quickly if they return (see How the Immune System Remembers, below).

T-cells also develop in the bone marrow and mature in the thymus into four cell types: helper, killer, regulatory and memory T-cells. Each responds to non-self antigens in different ways.

  • Helper T-cells identify non-self antigens and tell other immune system cells to coordinate with the B-cells for an attack.
  • Killer T-cells directly attack and destroy infected or cancer cells by releasing a protein that causes infected or cancerous cells to enlarge and burst.
  • Regulatory T-cells slow down the immune system after an immune response, and they inhibit T-cells that attack healthy cells that weren’t eliminated before leaving the thymus.
  • Memory T-cells recognize and respond to previously encountered non-self antigens, and do so very quickly. Memory T-cells stay alive in your blood for years, continuing to fight the same invading cells.

All of the white blood cells circulate throughout the lymphatic system carrying out each cell’s specific function. B-cells monitor for non-self antigens and alert the T-cells if they are found. T-cells then signal each other to attack and destroy the antigen. These parts must be able to alert each other and communicate messages so they can respond quickly to threats.

Most cells communicate by sending chemical signals. It’s important to know that the surface of a cell is not completely round and smooth. It is covered with receptors and proteins, which work like puzzle pieces. Proteins have “tabs” that stick out, and receptors have “spaces” that curve inward. When the puzzle pieces fit together (known as binding), chemical signals and information are exchanged in a biochemical reaction. Cells also contain various proteins, sugars, fats and other molecules that stick out of their surfaces. These components also contain information that is shared between cells. Thus, communication may occur when cells connect with each other through proteins and receptors on the surface. Alternatively, cells may also communicate by releasing chemical signals, which are called cytokines, when they signal cells of the immune system.

How Cancer Hides From the Immune System

An immune response begins when the immune system identifies an antigen as non-self. B-cells communicate to the T-cells that a threat has been identified. The B-cells make antibodies to flag the non-self antigen for the T-cells to attack. After being alerted by the B-cells, the T-cells produce more T-cells, then look for and destroy the non-self antigen. Once the antigen is gone, the immune system slows down to prevent the T-cells from attacking healthy parts of the body, and T-cells return to normal levels. Your doctor can use this information to determine if you have an infection because early after an infection, the white blood cells may increase, and then they return to normal when the infection is cleared. This can be easily measured by a blood test.

The immune system uses this same immune response process to recognize and eliminate cancer, but it becomes more complicated. Cancer cells are created by the body, so the normal ways to find and fight invading cells from outside the body aren’t always effective. Because cancer cells are created from our own cells, the immune system may have difficulty identifying cancer cells as non-self and may not coordinate an attack. If the body can’t tell the difference between tumor cells and normal cells, the tumor cells may be able to “hide” from the immune system. In addition, even if there is an initial immune response, it may be turned off by regulatory cells before the cancer is completely destroyed.

Cancer cells have also developed multiple methods to escape detection by the immune system. One way includes disguising themselves by producing proteins on their surface that mimic the proteins found on healthy cells. This makes them look like normal, healthy cells. If the cancer cells are successful, the immune system will be fooled and the cancer cells can continue to attack the body.

Another way includes creating chemical messengers to confuse communication between the immune cells. In some cases, they can trick the immune system into slowing down. This allows the cancer to take control of the process the body uses to regulate the immune response. So, even if the immune system recognizes the cancer, it may not be able to successfully start or maintain an attack long enough to kill the cancer cells.

Cancer cells aim to weaken the immune system. The longer they face a weakened immune response, the more they’re able to adapt and grow, and the easier it is for them to manipulate immune cells inside the tumor’s location, sometimes called the tumor microenvironment.

Immunotherapy offers the immune system reinforcements to keep up its fight against cancer in multiple ways by preventing the system from slowing down, boosting it with modified T-cells or combining it with chemotherapy or radiation therapy.

How the Immune System Remembers

One of the biggest strengths of the immune system is that it can develop immunity to an infectious disease so that the body doesn’t get sick a second time. This is known as immunological memory.

Both memory B-cells and T-cells are created when the body is fighting an antigen. Both remember the specific antigen and continue to circulate in the bloodstream, waiting for it if it ever returns. This provides long-lasting immunity to many different types of possible threats. Common examples include the measles and chickenpox. Once you have been infected with these diseases, you rarely get them again.

The immune system’s ability to recognize cancer cells when they try to return is a main goal of immunotherapy, and investigators believe that effective immunotherapy can result in cancer-specific memory cells. If the body can remember cancer and prevent it from recurring, this can lead to long-term, cancer-free remission and increased overall survival in a way that no other cancer therapies can.

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