The role of the immunologist in oncology

Liezl Heyman tells us how the immunologist helps in the fight against cancer.

As a cancer patient, you are very aware of the war you are waging on your cancer under the firm leadership of the general (oncologist) and his/her trusted lieutenants (surgeon, radiologist, histologist and pharmaceutical company) along with troops, such as chemotherapy nurses, pharmacists and admin staff. Did we forget someone? What about the immunologist? Of course, you’ve never heard of him/her, however, the immunologist plays an imperative role in your fight against cancer.

Enter the tumour microenvironment

A place hidden from everyone. Where one day, for one or more reasons, one of your normal body cells mutated into something potentially dangerous. 

In most people, the army of this microenvironment (your immune system), recognises the abnormal cell and sends out one or more types of lymphocytes (white blood cells), along with their supporting proteins and molecules, such as chemokines, cytokines, perforins and granzyme B to eliminate these mutant cells.  

In cancer patients, this process goes horribly wrong since some cancerous cells are trained assassins with skills and gadgets that will put James Bond to shame. Cancer cells evade the immune system, making it believe that they are harmless and not to be disturbed. 

I spy

Enter the immunologist; a scientist dedicated to finding the reasons for your specific immune system’s ignorance regarding your cancer. In doing this, the immunologist needs to identify biomarkers and checkpoints specific to your tumour, acting as the spy infiltrating the microenvironment looking for intel.

What are biomarkers?

Biomarkers are biological molecules found in blood, body fluid, or tissue and are signs of normal or abnormal processes, or of a disease.  There are three types of biomarkers supplying medical information to your oncologist regarding your cancer and the treatment thereof.

• Diagnostic biomarkers diagnose what type of cancer a patient has. For example, TTF1 which is positive in lung cancer patients.

• Prognostic biomarkers identify the favourable or unfavourable outcome of the cancer. For example, elevated levels of LDH which is associated with a worse prognosis.

• Predictive biomarkers give the probability of response to a particular treatment. For example, HER2 positive patients respond well to treatment with trastuzumab.

Immune checkpoints 

These checkpoints regulate the immune system. In the case of a cancerous tumour, lymphocytes need to increase their numbers, attack and destroy cancer cells and then reduce their numbers once more. 

In certain tumours, the checkpoints inhibiting the lymphocytes to increase their numbers are up-regulated, leaving them oblivious to the growing cancer cells. It’s in these cases that immunotherapy can be used as treatment to block those checkpoints, allowing lymphocytes to do what they are meant to do. 

An example is the discovery of the PD-1 checkpoint and its ligand PD-L1 subsequently, leading to the development of pembrolizumab, an immunotherapy to block this checkpoint, by three immunologists Hans van Eenennaam, John Dulos and Andrea van Elsas. This has greatly improved the survival of many patients with melanoma-, lung-, breast-, and bladder cancer, and the list is still growing. 

History of onco-immunology

We tend to think of onco-immunology as a recent advance but between 1878 and 1915, Paul Ehrlich, who developed chemotherapy, already made contributions to immunology. The first scientific attempts to harness the immune system to cure cancer were done by two German physicians, Fehleisen and Busch, who independently noticed significant tumour regression after erysipelas infection. 

In 1891, William Bradley Coley, attempted using the immune system to treat bone cancer. Over fifty years and several discoveries in the field of immunology, such as the discovery of T-cells and their crucial role in immunity in 1967, stepped up cancer research.

So, next time you watch a good spy movie, give a thought to the spy hidden in the laboratory spending many hours with the help of numerous techniques, such as ELISA, FEIA, Flow cytometry and more, to find the biomarkers and checkpoints specific to your cancer and last but not least: discovering new ones.