Immunotherapy has profoundly changed the way cancer is understood and treated. Instead of directly attacking tumor cells with chemical substances or radiation, this therapeutic strategy seeks to harness the patient’s own immune system to recognize and destroy the tumor. This approach has made it possible to achieve results that only a few years ago seemed difficult to imagine, especially in certain advanced cancers. The principle behind immunotherapy is relatively simple: the immune system already has the natural ability to identify abnormal cells and eliminate them. However, cancer cells develop mechanisms that allow them to evade or block that immune response. Immunotherapeutic treatments are designed precisely to remove those barriers and allow the body’s defenses to act against the tumor once again.
Many of the most important advances in this field come from the development of drugs known as immune checkpoint inhibitors. These therapies block proteins such as PD-1, PD-L1, and CTLA-4, which normally act as brakes on the immune system. By inhibiting these brakes, T lymphocytes can attack cancer cells more intensely. Clinical results have been impressive in various types of cancer, including melanoma, lung cancer, kidney cancer, and some gastrointestinal tumors. In many patients, immunotherapy has achieved prolonged responses that were not observed with traditional treatments. Despite these advances, immunotherapy is not free of side effects. In fact, due to its mechanism of action, many adverse effects are directly related to excessive activation of the immune system.
The so-called immune-related adverse events represent one of the main challenges of modern immunotherapy. These side effects occur when the immune system, being hyperactivated, begins to attack healthy tissues of the body. In essence, the treatment can trigger reactions similar to autoimmune diseases. This occurs because the immune checkpoints that normally protect the body against immune attacks are also involved in maintaining tolerance toward the body’s own tissues. When these control mechanisms are therapeutically blocked, the immune system can lose part of that balance. As a result, different organs can be affected. Among the most common are the lungs, liver, colon, skin, and various endocrine glands. In most cases, these complications can be controlled with medical treatment, especially if they are detected early.
One of the potentially most serious side effects of immunotherapy is immune-mediated pneumonitis, an inflammation of lung tissue caused by excessive immune system activity. Patients may experience symptoms such as difficulty breathing, persistent cough, or a feeling of shortness of breath. These symptoms can be confused with common respiratory infections, so it is important to perform a careful evaluation to determine their origin. Distinguishing between pneumonitis and pneumonia is particularly important, since the treatments are different. While pneumonia is usually treated with antibiotics, pneumonitis related to immunotherapy generally requires immunosuppressive medications, such as corticosteroids. Early detection is key to preventing serious complications.
Endocrine glands can also be affected by immune system activation during treatment. The thyroid is one of the structures most frequently involved. Some patients develop thyroid inflammation that initially causes an increase in the release of thyroid hormones. This may produce symptoms such as anxiety, nervousness, palpitations, or increased heart rate. Over time, the destruction of thyroid tissue can lead to decreased hormone production, generating symptoms such as extreme fatigue, weight gain, or sensitivity to cold. Other endocrine glands that may be affected include the pituitary gland and the adrenal glands. These alterations can produce significant hormonal changes that require specialized treatment. For this reason, patients receiving immunotherapy usually undergo periodic monitoring of hormonal function through laboratory tests.
Among the most frequent side effects of immunotherapy are skin manifestations, such as rashes, dryness, or intense itching. Although these symptoms may seem relatively mild from a medical perspective, they can be extremely bothersome for patients and affect their quality of life. Localized rashes are usually treated with corticosteroid creams and antihistamines. However, when itching becomes generalized and persistent, it can be difficult to control. In some cases, alternative treatments have been explored. One interesting example is the use of aprepitant, a medication originally developed to prevent nausea induced by chemotherapy. This drug has shown usefulness in certain cases of severe itching associated with immunotherapy. These types of strategies demonstrate how the management of side effects continues to evolve as physicians gain more experience with these treatments.
In some rare situations, immunotherapy can cause a rapid and massive destruction of cancer cells. This phenomenon can trigger a complication known as tumor lysis syndrome. When large numbers of tumor cells die in a short period of time, they release their contents into the bloodstream. As a result, significant alterations occur in the levels of certain minerals and chemical substances in the blood. Among the most characteristic changes are increased potassium and phosphorus, decreased calcium, and increased uric acid. These alterations can seriously affect kidney function and, in severe cases, lead to kidney failure. Fortunately, tumor lysis syndrome can be detected through laboratory tests and treated effectively, generally through intravenous hydration and careful control of electrolytes.
Another important complication associated with some immunotherapy treatments is cytokine release syndrome. This syndrome occurs when immune system cells release large amounts of inflammatory molecules called cytokines during the response against cancer. When the release of these molecules is excessive, it can trigger a systemic inflammatory reaction that affects the entire body. Symptoms may include fever, extreme fatigue, loss of appetite, low blood pressure, confusion, or neurological alterations. In some severe cases, the syndrome can become life-threatening. Recent research has identified specific molecules, such as interleukin-1 and interleukin-6, as key players in this inflammatory process. Thanks to these findings, targeted treatments have been developed that block these molecules, helping to control the inflammatory reaction in severe cases.
A phenomenon that has raised concern among researchers is the so-called tumor hyperprogression. In some patients treated with immune checkpoint inhibitors, the tumor may grow more rapidly after treatment begins. This phenomenon must be distinguished from pseudoprogression, a situation in which the tumor appears to increase in size temporarily due to the infiltration of immune cells before it begins to shrink. In hyperprogression, tumor growth is real and may be much faster than before treatment. Although the causes of this phenomenon are still not completely understood, some studies suggest that certain genetic changes or interactions with immune cells in the tumor microenvironment may be involved. Understanding these mechanisms will be fundamental for identifying which patients will benefit most from immunotherapy.
Figure 1. Immunotherapy stimulates the immune system to enhance its ability to recognize and attack tumor cells. However, this immune activation can extend beyond the tumor microenvironment and affect normal tissues. The figure illustrates how systemic immune responses triggered by treatment may involve multiple organs and biological processes, highlighting several clinically relevant immune-related complications that can arise during cancer immunotherapy.
Many side effects of immunotherapy appear when the patient is outside the hospital. For this reason, patient education is a key aspect of treatment. Patients must remain attentive to any changes in their health, including difficulty breathing, persistent fever, unusual fatigue, digestive problems, or hormonal alterations. Reporting these symptoms early allows intervention before complications become more severe. Likewise, regular medical follow-up through blood tests and clinical evaluations is essential for detecting alterations before they produce obvious symptoms.
Immunotherapy represents one of the most important advances in modern medicine. By harnessing the power of the immune system, these treatments have opened new possibilities for fighting cancer. However, stimulating the body’s defenses also involves certain risks. The same immune system that can destroy a tumor can also cause inflammation or damage in normal tissues. The current challenge for medicine is to find the right balance between activating the immune system enough to fight cancer, but without triggering serious adverse effects. As new drugs, therapeutic combinations, and monitoring strategies are developed, immunotherapy will likely continue improving its safety profile. In the coming years, better understanding how to control these immune responses will be key to further expanding the impact of immunotherapy in cancer treatment.
In the current medical setting, immunotherapy is generally considered a safe and manageable treatment when used under appropriate clinical supervision. Most immune-related adverse events can be identified early and controlled with established treatment protocols, often involving temporary discontinuation of therapy and the use of immunosuppressive medications such as corticosteroids. Nevertheless, the safety of immunotherapy depends strongly on careful patient selection, close monitoring, and rapid response to emerging symptoms. As physicians gain more experience with these therapies and clinical guidelines continue to evolve, the ability to balance therapeutic benefit with the management of immune-related toxicity has steadily improved.
Main reference:
Williams, J. R. (2019). The immunotherapy revolution the immunotherapy revolution: The best New Hope for saving cancer patients’ lives. Independently Published.
