What is immunotherapy and how does it work?
Activating the Immune System in the Fight Against Cancer
There's an imposter in the mix...
Cancer cells are notorious for hiding and masquerading as healthy cells to the immune system. They are posers. Fakes. Liars. Tricksters. They send misleading signals and convince immune cells to ignore them, concealing the threat they pose, and immune cells fall for it and move along, cancer left alone.
Immunotherapy acts as a truth serum of sorts with cancer cells. It doesn't force cancer cells to tell our immune system the truth, per se, but immunotherapy drugs can block the lies they tell and make it easier for the immune system to see what's really going on. When cancer's ability to deceive is obstructed, the immune system can more accurately assess threats and work as it naturally would to patrol for and destroy pathogens.
Immunotherapy enhances and unleashes the immune system, allowing it to destroy cancer cells using the body's natural immune mechanisms.
Types of Immunotherapy
- Immune Checkpoint Inhibitors
- Monoclonal Antibodies (includes bispecific and conjugated antibodies)
- Adoptive Cell/Immune Cell Therapies (includes CAR T cell therapy and tumor-infiltrating lymphocyte (TIL) therapy)
- Immune System Modulators (includes cytokines)
- Vaccine Therapy
- Oncolytic Viruses
Cancer cells have devised many ways to protect themselves from the immune system. Another example is the tumor microenvironment (TME), a protective and nourishing region surrounding a tumor that can block immune cells from coming in and gaining access to cancer cells.
How do Checkpoint Inhibitors Work?
One Hallmark of Cancer is immune system evasion (Hanahan & Weinberg, 2011). T cells are special immune cells called T lymphocytes, a type of white blood cell that is responsible for fighting infections and cancer. Within the immune system, there are special proteins that signal T cells to deactivate. Calm down. Chill out. Knock it off. This is an important safeguard because if T cells are overactive, they can begin to attack the body's tissues which can lead to a number of autoimmune issues and disorders.
In the case of cancer, however, these proteins can be problematic and stop a T cell from doing what it needs to do to eradicate cancer. Some cancer cells pump out these proteins in abundance, protecting themselves from attack by T cells. When a checkpoint inhibitor is introduced, it blocks these proteins and their "deactivation" signals, and allows T cells to operate as they normally would. In summary, the presence of these proteins allows cancer cells to hide from the immune system, and blocking these proteins (using checkpoint inhibitors) uncloaks cancer cells and makes them visible and vulnerable to immune system attack. PD-L1 and CTLA-4 are two examples of checkpoint proteins that may be overexpressed by cancer cells.
The generic names of monoclonal antibodies, including checkpoint inhibitors, end in -mab (for monoclonal antibody)
How Does CAR T Cell Therapy Work?
Blood is taken from a patient to harvest their T cells, immune cells that are capable of killing cancer cells. In a lab, the T cells are genetically modified to produce CARs (chimeric antigen receptors), special proteins that can attach themselves to proteins on cancer cells. These enhanced T cells are then multiplied by the millions and re-introduced to the same patient. Newly equipped and “educated,” the T cells are better able to identify and destroy any cancer cells they encounter in the body. CAR T cell therapy is used primarily for hematologic cancers, but research is ongoing for use in solid tumors.
Why is immunotherapy only for select cancer patients?
A high tumor mutational burden or genomic instability in a tumor can make it more difficult for cancer cells to hide from T cells, whereas a cancer with a lower mutational burden (TMB <10 mutations/megabase) can more easily masquerade as "normal" and avoid immune detection and destruction. Think of it this way, the more cancer cells become abnormal and "funky" due to mutations, the easier it is for immune cells to spot and attack them. Tumors that have a high mutational burden (TMB), microsatellite instability (MSI/dMMR), or overexpression of PD-L1 may be good matches for immunotherapy, according to City of Hope.
You can check this list from Cancer Research Institute to see what types of immunotherapy are available for your cancer type. Speak to your doctor to determine if you are eligible for immunotherapy and to understand the associated risks, benefits, and side effects.
Wait a minute. Something is not quite right here.
How does immunotherapy work? (Checkpoint Inhibitors)
How does immunotherapy work? (CAR T Cell Therapy)
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