Engaging the Immune System
Immunotherapy — using the immune system to fight cancer—is one of the fastest growing fields in cancer research.
What do scientists mean when they talk about the immune system? First of all, the term “immune system” covers a lot of territory including different kinds of cells, antibodies, and proteins. Think about the immune system like the security system of the body including the neighborhood watch, the private security companies like ADT, the more specific systems like police, fire, and emergency medical services, and, ultimately, the National Guard and armed forces. In general there are two components to the immune system: one is nonspecific and local and the other is more specific and systemic. The nonspecific local cells hang out at places where our body interacts with the outside world: skin, mouth, GI tract, lungs, vagina, and liver. If there is a threat, such as a splinter or virus, they immediately check out the intruder and sound the alarm. These cells are the neighborhood watch: figuring out what the problem is and calling for help, primarily from specialized white blood cells called neutrophils and macrophages. If the infection is not too serious, the local defenses may be able to do the job without the heavy reinforcements.
Scientists have long wondered why the immune system doesn’t recognize cancer cells as bad and kill them
But what if they don’t? The next level of defense is the antigen presenting cells, also known as dendritic cells. This is the more specific and systemic part of the immune system. These cells asses the situation and bring the problem to the lymph nodes. In the lymph nodes, T cells and B cells (the ones that remember threats you’ve faced) check to see if they recognize the current threat and, if so, react with specific antibodies (B) or direct cellular attacks (T) to get the job done. This is how a vaccine works. You receive, for example, part of a virus (polio, flu, etc.) so that your body will know what it is and how to fight it if you encounter it again. This is an example of how the innate immune system (non-specific neighborhood watch) interacts with the adaptive immune system in the lymph nodes to deal with infections. How does this relate to breast cancer? Scientists have long wondered why the immune system doesn’t recognize cancer cells as bad and kill them before they can make you sick, or worse. The relationship between cancer cells and the immune system is complicated. Cancer cells originally come from normal cells that developed mutations. And because they started out as normal cells, they have ways of escaping recognition by the adaptive immune system. This immune escape is achieved through a number of mechanisms, which include both direct interference with the cells of the adaptive immune response and indirect immunosuppression achieved through modification of the tumor microenvironment or neighborhood. The cancer cells that survive are the ones that have learned how to avoid or block the immune surveillance.
There are different ways to engage the immune system. They include:
The immune system is able to recognize normal cells and leave them alone. It does this by having special codes that will turn it off when it is not needed. When this failsafe system doesn’t work, the immune system starts to attack normal organs and actually cause people to develop autoimmune diseases. Examples of this include inflammatory bowel disease, rheumatoid arthritis, some kinds of thyroid disease, and skin diseases. These checkpoints are important but just like any security system they can be blocked, tricked, or overridden. This is what cancers do: they suppress or block the immune system so they can divide and grow with impunity. CTLA-4 is one of these blockers, and the immunotherapy drug ipilimumab (Yervoy), which is approved for treating metastatic melanoma, works by blocking CTLA-4. Other drugs are being developed that focus on T cells with a PD-1 receptor that must link with the tumor in order to cause an immune response. Tumors can secrete a PDL-1 signaling protein that links to the PD-1 receptor and tells the immune system that everything is ok. There are new drugs that block either PDL-1 or PD-1 so the immune system is alerted that cancer cells are present. Pembrolizumab (Keytruda) is an anti-PD-1 immunotherapy approved for treating metastatic melanoma that has a genetic mutation called BRAF V600. It is also being studied in patients with triple negative breast cancer You can find information about clinical trials studying checkpoint inhibitors here.
Another immunotherapy approach involves vaccinating you against your own cancer cells. The vaccines being developed are made with antigens found on breast cancer cells, such as Her2-neu, and then given to women after their initial treatment in an attempt to prevent recurrence. Another effort at a vaccine uses mammoglobulin, a protein found on breast cancer cells. Finally, there is the possibility that you could prevent cancer in the first place by vaccinating against the cause of the mutation. This is what the HPV vaccine does to prevent HPV-related cancers, which include cervical, mouth, and anal cancer. You can find information about clinical trials studying vaccines for prevention, to reduce recurrence, and to treat breast cancer here.