Many people would be familiar with therapies to treat cancer including chemotherapy, radiation, surgery and even targeted therapy. There has been excitement and news of boosting or harnessing the immune system as treatment in some cancers. Immunotherapy is a type of treatment that increases the strength of the body’s own immune system to fight cancer. There are various ways of doing this with monoclonal antibodies, adoptive cell transfer, cytokines, vaccines and immune checkpoint inhibitors. Most of the recent news refers to immune checkpoint inhibitors such as Ipilumumab, Pembrolizumab, Nivolumab and other drugs.
Whenever the immune system is activated or stimulated, there are checkpoints with complex signals that prevents the immune cells from attacking and destroying normal, healthy tissue. Some cancer cells use these particular checkpoints to brake the immune system and mute the immune response.
Studies in melanoma had led the way but increasingly, the treatment seems to be active across various tumour types including non-small cell lung cancer (NSCLC) especially squamous cell carcinoma of the lung, kidney cancer (renal cell carcinoma), triple negative breast cancer, colorectal cancer with mismatch repair deficiency, bladder cancer, cervix cancer and others. Some of these are in early phase trials; some are already being used clinically.
It is not uncommon for oncologists to hear from patients or relatives the following:
“This herb will improve your immunity to fight cancer”
“Exercise will boost your immune system to combat cancer”
“This supplement works with your cancer treatment as it increases your immunity against cancer”
How is the immune system involved in cancer risk? Is immunotherapy, or using the immune system to combat cancer possible? What is the basis of immunotherapy as a branch of immune-oncology?
There is evidence that a poor immune system increases the risk of cancer.
Patients with HIV infection which causes acquired immune deficiency syndrome or AIDS have an impaired immune system. They are also more likely to develop a range of malignancies such as non-Hodgkin lymphoma, cervical cancer, Kaposi’s sarcoma. They are also at an increased risk for anal, liver cancer, Hodgkin lymphoma and lung cancer. It turns out that patients with HIV infections have a weakened immune system and they are more prone to certain viral infections such as human herpesvirus 8 (HHV-8) which causes Kaposi sarcoma for example. They can also have hepatitis B, hepatitis C, Epstein Barr virus (EBV), human papillomavirus (HPV) virus infection.
Kidney transplant patients are at a 2 to 3 fold risk of developing cancer compared to the general population that is matched for age and sex. This is related to the immune suppression that is needed post transplantation, time on dialysis prior to transplantation and exposure to viral infections as well. The outcome of kidney transplant recipients with cancer seems worse compared to patients with cancer in the general population.
Chronic inflammation increases cancer risk
Chronic inflammation involving activation of the immune system is related to developing cancer in many conditions. Chronic smoking is well known as it causes the lining of the airways or bronchus to change resulting in bronchitis and lung cancer. Other substances causing asbestosis or silicosis are also related to lung cancer. Inflammatory bowel diseases such as Crohn’s disease or ulcerative colitis cause inflammation of the lining of the gut resulting in increased risk for cancer. Skin cancer such as melanoma is related to UV irradiation-associated skin inflammation.
Several important points have emerged
Subclinical or undetectable inflammation may also be important in increasing cancer risk.
Various types of immune cells may be seen as inflammatory infiltrates in tumours.
Immune cells produce chemicals known as cytokines. These cytokines act to activate cells to grow and react, sometimes to an infection.
The cytokines produced in an inflammatory response may affect tumour formation, growth and even spread. This happens particularly if the process is chronic and uncontrolled.
The various elements involved in the immune system defending or even promoting cancer is therefore complex. A fairly general statement on improving immunity to fight cancer is oversimplifies some of the details that are beginning to emerge.
Dr Peter Ang
MMed (Int Med)
FAMS (Medical Oncology)