The immune system is the body’s instrument for combating pathogens and damaged cells. The ability of the body’s own defense system to be used in cancer cells has now been successfully exploited in some cancer diseases. Cancer immunotherapy is regarded as a great hope in cancer treatment. However, despite impressive successes, particularly in the treatment of black skin cancer and advanced lung cancer, science still faces challenges.

Only a few years ago, immune therapy was able to achieve limited success in fighting against cancer. The idea of fighting cancer cells with the help of one’s own immune system is more than one hundred years old. In 1867, the Bonn surgeon Wilhelm Busch placed a woman suffering from cancer in the empty bed of a patient with a wound rose. Shortly afterwards, the life-threatening tumor in the woman’s throat shrank. Medical history was written.

However, it was not until the 21st century that the manifold interactions between cancer cells and the immune system were sufficiently investigated to break new ground in cancer therapy.

How cancer hides from the immune system

The immune system reliably destroys substances that can damage the body. In general, there are two variants of the immune response: the innate immune system is non-specific to all pathogens and fends off the majority of infections. The acquired immune response reacts with the help of T and B cells to certain structures of pathogens and cells, so-called antigens. T cells are equipped with antigen receptors on their surface with which they can recognize and destroy antigen-bearing cells. The acquired immune system has a memory that enables it to recognize and react to an antigen with which it has already had contact.

Cancer cells must have characteristics on their cell surface so called tumor associated antigens (TAA) which make them recognizable for the immune system. However, many tumor types have developed strategies to conceal their malignant identity by, for example, not presenting antigens or making them appear to be autologous.

How does immunoncology work?

A central starting point of immunoncology are checkpoints, so to speak control points of the immune system, which are located on the T-cells and normally prevent an excessive immune reaction. However, cancer cells can succeed in using this mechanism to camouflage themselves. Checkpoint inhibitors break down the blockade caused by cancer and stimulate the immune system to recognise and destroy tumour cells. The first drug to be approved in 2011 was the checkpoint inhibitor ipilimumab for the treatment of black skin cancer. As a further checkpoint inhibitor, nivolumab has been available as a drug for advanced lung cancer since 2015, as it has significantly improved life expectancy in clinical trials.

Side effect: autoimmune reaction

In immunotherapy, it is crucial to find a balance between stimulation and inhibition of the immune system in order to avoid the negative consequences of an overactive immune system – such as autoimmune diseases. Due to alterations of the immunological defence, considerable side effects can occur: Inflammations of the pituitary gland, the eyes, the intestines or the skin, so that the treatment has to be stopped in some patients.

The Cancer Care doctors also have headaches about the response rate. It is still unclear why immunotherapy does not work for some patients. In tissue samples taken from the tumor, research is being carried out into features that can predict whether the patient can be immunoncologically treated, for financial reasons alone. After all, the costs of approximately 150,000 dollars per patient are very high.

The future of immunotherapy

Current research focuses on mobilizing immune systems against cancer in order to generate long-term success. Promising immunoncological drugs are already in the starting blocks for kidney cancer and malignant lymphoma. In addition to the activation of T cells by checkpoint inhibitors and bispecific T cell activating antibodies, the approach of adoptive T cell therapy is another promising strategy. Here, T cells are removed from the patient’s body in order to equip them ex vivo with tumour-specific T cell receptors so that they can act effectively against the cancer cells. The chimeric antigen receptor (CAR) therapies, in which peripheral T cells of the patients are genetically modified with a chimeric antigen receptor and the modified T cells are subsequently returned to the patient’s body, are also promising. There, the altered T cells “search” for the corresponding antigen, e.g. the antigen CD19, which is carried by most B cell malignancies, in order to dock and destroy them. In several anti-CD19-CAR T cell transfer therapy studies, a remission rate of 30-90% was achieved in patients with acute pre-B cell leukemia (ALL), chronic lymphocytic leukemia (CLL) or B cell malignancies.

However, the challenges of cancer treatment in India are not only focused on developing new drugs, but also on investigating whether the combination of immunotherapies with conventional cancer treatment methods, such as radiation and chemotherapy or the coupled application of two immunotherapies, can lead to lasting improvements in cancer treatment success. However, many details about the complex mechanisms of the immune system have yet to be learned at the molecular level before most cancers can be effectively fought with the body’s own defense system.