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Cancer Topics

Harnessing the Immune System to Fight Cancer Part 2 -Immunotherapy
Harnessing the Immune System to Fight Cancer Part 2 -Immunotherapy

Introduction

As discussed in Part 1, immune surveillance is important in preventing cancer. It was noted more than 100 years ago, that cancers had immune cells around them known as lymphocytes or tumour infiltrating lymphocytes (TILs).

In the simplest description, the process of developing cancer first starts when normal cells become damaged, and our body is unable to either repair them, or to kill them. These cells accumulate damages, or mutations, and eventually find a way to be able to grow independently. The immune system is often able to identify and destroy abnormal cells before they develop into cancer cells, which explains the observation of TILs. However, this safeguard fails when the cells develop strategies, or disguises, to evade the immune system.

While there are many different forms of immunotherapy, the current use of the word “immunotherapy” is synonymous with the use of check point inhibitors such as Keytruda (Pembrolizumab) and Nivolumab (Opdivo). Checkpoint inhibitors counteract cancer signals that suppress the immune system, in other words, remove the disguise which has protected them.

Who might benefit from such treatment?

Historically, immune cells have been found around cancers such as melanoma and kidney cancer, and early use of general immune therapies such as interferon and interleukin have some benefit in some of these tumours. These early therapies boost the immune response, but the vast majority of these patients did not respond to treatment, as they did not have a problem of a low immune system, but an immune system that was unable to recognise the cancer. The use of checkpoint inhibitors have been very successful in melanoma and urothelial (bladder and kidney) cancer, and they were first approved for use in these cancers.

Subsequently, more results from studies now show that immunotherapy may be effective in a wide variety of other cancers, including lung cancer, colon cancer, gastric cancer, oesophageal cancer, liver cancer, cervical cancer, endometrial cancer, breast cancer, and cancer of the head and neck.

Further analyses showed that specific groups of patients tended to respond more than others. These groups of patients have cancers that carry a higher number of mutations, allowing the body’s immune system to more easily identify them after the suppressive signals are taken off by checkpoint inhibitors.  An example includes smoking-related cancers such as lung cancer. This is due to chemicals in cigarettes resulting in extensive accumulation of mutations in cancer cells. Another group of patients who may respond well are those with strong family history of cancer, and may have hereditary cancers such as Lynch syndrome. This is because these patients have a deficiency in repairing defective cells. While this gives rise to a higher risk of developing cancers such as colon cancer, gastric cancer, bladder cancer, cholangiocarcinoma, and also endometrial cancer, it also means that immunotherapy is more effective, again due to chronic build-up of mutations in the cancer cells.

Your Oncologist will advise on tests such as MSI (Microsatellite-Instability) testing, as well as PDL1 (Programmed Death-Ligand) expression testing to assess the degree of benefit from checkpoint inhibitors.  Should a hereditary cancer be suspected, genetic counselling will also be done, as well as advice on screening for family members.

What are the potential advantages and side effects of the treatment?

Immunotherapy has fewer side effects relative to chemotherapy. Most patients tolerate checkpoint inhibitors very well. The most common symptoms include flu-like symptoms, manageable fatigue, diarrhoea and rash. These can often be controlled effectively with supportive medication. Hormonal imbalance, for example, thyroid hormones, may occur, and will be monitored while on treatment.

However, a small proportion of patients, approximately 10%, may develop serious side effects. This is because the immune system ends up attacking normal cells uncontrollably and extensively. Severe side effects include pneumonitis, hepatitis, nephritis and colitis (inflammation of the lung, liver, kidney and intestines, respectively).  Patients with a history or family history, of autoimmune diseases, such as rheumatoid arthritis, SLE (systemic lupus erythematosus), are at higher risk of severe side effects.

Should severe and unmanageable side effects occur, the effects of checkpoint inhibitors may be reversed by giving immunosuppressive doses of steroids or other immunomodulation drugs.

 

“Expert knowledge means better care for cancer”

 

Written by:

Dr Peter Ang  Dr Thomas Soh
MBBS (Singapore)  MBBS (Singapore)
MMed (Int Med) MRCP (United Kingdom)
MRCP (UK)
FAMS (Medical Oncology)