By: Cornelia Redel
The novel coronavirus SARS-CoV-2, which causes the COVID-19 disease, has been all over the news lately. It has caused us to physically distance ourselves from loved ones in order to keep them safe. Older adults and individuals with pre-existing conditions, such as obesity, asthma, and diabetes are especially at risk of experiencing a severe progression of the disease. The common factor between these groups? A compromised immune system.
How does this relate to cancer?
Cancer treatment impacts the immune system. But what does it mean to be immunocompromised? How does cancer treatment lead to weakening of the immune system?
To answer these questions, we first need to take a closer look at our immune system.
What is the immune system?
We have two types of responses within our immune system: the innate and the adaptive immune response.
The innate immune system is the first line of defense against invading viruses, bacteria, or parasites (collectively called pathogens). We have an innate immune system from birth and all throughout our life.
The innate immune system operates at multiple levels. The first obstacle that pathogens face when they encounter us is our skin or the mucus-producing surfaces of our nose, throat, and lungs. These physical barriers are crucial to keep our body’s immune system as unoccupied as possible.
In case a pathogen manages to cross this hurdle, the next line of defense in the innate immune response will be engaged. The innate immune response consists of a diverse group of “first responders”, where the smallest elements are proteins known as complement. These proteins act as a “glue”, and they can identify and trap pathogens to prevent their immediate spread through the body. Once this happens, immune cells like macrophages and natural killer cells get activated. These cells will travel to the site of infection, then eat and kill the pathogens that have been trapped by complement.
Immune cells of the innate system will then alert the body that intruding pathogens have been detected by causing inflammation, which triggers a secondary response through our adaptive immune system.
You may have heard of ‘B’ and ‘T’ immune cells. These are the major players in our adaptive immune system.
The innate immune system is meant to react broadly to any type of pathogen entering the body, whereas the adaptive immune system “adapts” to each specific intruder, as the name suggests.
Although both are highly specific, B- and T-cells follow slightly different patterns in their recognition of pathogens.
T-cells are immune cells that display so-called T-cell receptors on their surface. Receptors in general are proteins on the cell surface that can help cells interact with their environment or even other cells in their vicinity. T-cell receptors, in particular, function like a lock. The lock is highly specific to exactly one key. This key is created when a macrophage eats a pathogen. The macrophage will present small digested parts of the invading species on its own surface receptor and test this “key” on the nearby T-cells to see whether any of them fit. If there is a fit, the macrophage will unlock the T-cell’s full potential which triggers the T-cell to multiply and kill the infected cells as well as recruit other helpers, B-cells among them.
B-cells, though similar to T-cells in some ways, operate in a more distant fashion. B-cells give rise to proteins called immunoglobulins, more commonly known as antibodies. Antibodies can be both attached to the cell surface of B-cells or secreted. These antibodies are specific for only one pathogen, similar to T-cell receptors. At the site of infection, the secreted antibodies are able to specifically bind to the invading pathogen, and “glue” them together. Thereby antibodies are able to prevent the spread of a certain pathogen throughout the whole organism.
Overall, the innate and adaptive immune systems work tightly together to ensure that pathogens do not enter and spread in our body.
What does cancer treatment do to our immune system?
During cancer treatment, physicians aim to target the fast dividing cells as well as the cancer stem cells residing in the tumour. This is usually achieved by using chemo- or radiotherapy or in some cases, a combination of both.
Chemotherapy is administered systemically, which means it is distributed by the bloodstream all throughout the body. Therefore, it will also affect other proliferating cells and stem cells.
One group of stem cells are bone marrow stem cells that divide and form the cells of the innate and adaptive immune system. Chemotherapy might also target these stem cells and thereby affect the production of immune cells.
Other stem cells that are affected by chemotherapy are intestinal as well as skin stem cells, whose disruption can cause side effects such as hair loss, nausea, and fatigue. That said, it is necessary to mention that different chemotherapies affect the immune system to varying extent and that the physician prescribing the therapy will point out these risks.
The decreased number of produced immune cells leads to an increased risk of contracting infections and other diseases.
Patients experiencing adverse effects of their chemotherapy on their immune system are referred to as immunocompromised or immunosuppressed.
Radiation therapy can have a similar effect on the immune system, although it is less common, as radiation is usually delivered locally. Moreover, the treatment is usually optimized to spare bone structures and thus reduce the exposure of bone marrow stem cells.
In order to restore the immune system of immunocompromised patients, they may receive stem cell transplants. These are fluids taken from the bone marrow of either themselves before treatment, a twin, or another person that has a compatible immune cell system as the patient.
The treatment is administered through the bloodstream and stem cells in these transplants find their way back to their original home, the bone marrow.
Receiving a stem cell transplant enables an immunocompromised person to produce a new immune system with cells of both the innate and adaptive immune response. This will help them recover from the treatment as well as protect them again from any pathogen trying to enter their system.
What happens with COVID-19?
For the duration of their therapy, cancer patients are particularly vulnerable to infections. Therefore, the current pandemic poses a greater threat to them than the general population.
First results looking at the epidemiology of COVID-19 disease in China showed that persons with a current cancer diagnosis were more likely to experience a severe progression of the disease compared to cancer survivors or individuals without a cancer diagnosis. In particular, those with blood malignancies will be at risk as their treatment regimen will have the most profound impact on their immune system.
Typically, the virus will invade the body through the nose, where it finds cells that express a specific receptor, called ACE2. SARS-CoV-2 will attach to this receptor and enter the cell. It then uses the replication machinery of the cell to multiply itself, reproducing its own proteins in order to form more virus particles.
The infected cell will try to alarm the immune system by displaying virus particles, however, since this virus is new to the host T-cells, they will not recognize the infection immediately. This gives the virus time to travel further down into the lungs of the infected person.
For the majority of healthy patients, this would have been enough time for their adaptive immune system to develop SARS-CoV-2 specific T-cells that can prevent a spread in the lungs and throughout the rest of the body. These patients will be mostly asymptomatic carriers as their bodies fight off the infection.
For infected individuals that have a weak or no immune system, and cannot form a T-cell response, the intrusion into their lungs can be fatal. Therefore, immunocompromised cancer patients have to be particularly careful to not contract an infection.
What can we do?
As a community, we are all responsible for keeping immunosuppressed members in the community safe. That means, staying at home and reducing the spread of the disease, starting with keeping our distance. The droplets in which the virus is traveling between people can only go so far before gravity brings them to the ground.
Another point is frequently washing our hands to eliminate any virus particles that are residing on them. The fallen virus particles will also be lying on surfaces that we touch. Washing our hands and avoiding touching our eyes, nose, and mouth prevents the virus from infecting us. Most importantly, according to Health Canada, we should isolate ourselves and contact a healthcare professional if we are experiencing symptoms such as fever, cough, or difficulty breathing.
Following this public health advice is our best strategy to protect our most vulnerable, like immunocompromised cancer patients, that do not have any other form of immunological defense.
Murphy, K. & Weaver, C. Janeway’s Immunobiology. Garland Science (Garland Science, Taylor & Francis Group, LLC, 2017). doi:10.1007/978-981-10-2116-9
Liang, W. et al. Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China. Lancet Oncol. 21, 335–337 (2020).
Cornelia obtained a B.Sc. and M.Sc. in Biochemistry from the Julius-Maximilians Universitaet of Wuerzburg, Germany. Currently, she is a Ph.D. student in the Department of Medical Biophysics at the University of Toronto where she is studying how the cancer driver protein called MYC is turned over in normal tissue and which mechanisms stabilize it in cancer.