Immunotherapy: how it works

Acting on the immune system to change the environment where the tumor grows and fight it: this is the strategy of immunotherapy.

The goal of immunotherapy is to fight cancer by stimulating the immune system, our body’s natural defense system.

Immune system cells usually activate against anything they recognize as “foreign”, for example infected cells and tumor cells, with the purpose of eliminating them. However, in the case of tumors, the mutated cells use a number of tricks to bypass the immune system’s control system. By evading the immune system mechanisms of recognition, the neoplastic cells increase in number, modify their characteristics and acquire the ability to invade our body's sites at a distance from the organ of origin of the primary tumor.

Cancer immunotherapy has demonstrated to block this tumor cell self-masking mechanism, so that the immune system is no longer cheated and can resume its fight against the tumor.

A key achievement in the development of cancer immunotherapy was the discovery of immune checkpoints, i.e. molecules involved in the tumor escape mechanism to avoid the immune system’s control.

Immunotherapeutic drugs currently used in clinical practice are monoclonal antibodies inhibiting immunological checkpoints. These drugs, by stopping the activation of T lymphocytes, are able to reactivate the anti-tumor immune response.

Differences between immunotherapy and traditional therapies

Over the last few years, immunotherapy has led to a real revolution in the treatment of different forms of cancer, allowing to highlight both objective responses, ie reduction of the tumor mass, and the increase of survival compared to traditional therapies such as chemotherapy, radiotherapy and target therapies. Since immunotherapeutic drugs do not act on tumor cells directly but stimulate the immune system’s defense mechanisms, their benefit may become apparent after a longer time period than with other therapies: in certain cases, 16-20 weeks may be required before a response is observed.

Experience with the use of these drugs has allowed to highlight types of unconventional treatment response compared to what is typically found with traditional therapies. With immunotherapy, it is not uncommon to note an initial growth of tumor mass, which is then followed by tumor regression.  Another feature of these treatments is the so-called immunological memory, according to which a number of immune responses and certain forms of disease stability continue for a long time, with a positive impact on patient survival. Traditional cancer therapies normally show less durable responses as they can quickly select drug-resistant tumor cells. Even the side effects of immunotherapy show major differences as compared to those of other cancer therapies, such as chemotherapy, that are often associated with nausea, vomiting, hair loss, infections and neuropathies. The side effects of immuno-oncology treatments, by virtue of the different mechanism of action, are related to inflammatory reactions generated by these drugs that are directed against the healthy tissues of the body, causing for example temporary inflammation at gastrointestinal and cutaneous level. Potentially all organs and tissues of our body may be affected by the side effects of immunotherapeutic drugs, and it is therefore essential a careful and adequate management of the patient who undergoes these treatments.

In most cases, the side effects of the immunotherapy drugs are mild or moderate, and these treatments are generally better tolerated than chemotherapy and target therapies. More important reactions may occur, particularly in cases where adverse events are not recognized and treated appropriately at an early stage. It is therefore essential to correctly inform patients in immunotherapeutic treatment and their families, aimed at the recognition and early report of signs and symptoms of side effects. Normally side effects can be easily managed by physicians using specific therapeutic measures. In most cases, as in other circumstances, a direct relationship between patients and their doctors is essential to manage toxicities and implement the most appropriate treatment.

In general, there are no absolute contraindications to immunotherapy. However, there are conditions in which the relationship between the potential benefit of these treatments and the risk related to their administration may not be favourable or is less well known, such as in cases of pre-existing autoimmune diseases in the active phase that need causal treatment, of steroid or chronic immunosuppressive therapy or chronic viral infections.

In any case, the decision to suggest immunotherapy should be made by the physician following a careful case-by-case evaluation to propose immuno-oncology therapy to the patient, both for standard clinical practice and for clinical trials, ie controlled clinical trials in the scope of which innovative immunological treatments are used in order to improve the opportunities for the treatment of cancer patients.