One of the greatest challenges in modern medicine is learning to control the power of the immune system itself. Cancer immunotherapy has shown that, by releasing certain natural brakes, our defenses can attack tumors with an effectiveness that once seemed impossible. But this same strength brings with it a challenge: how can we prevent the immune system, once activated, from turning against the body itself? This is the central dilemma of modern immunotherapy, and corticosteroids play a role in it that is as necessary as it is controversial.

Immune checkpoint inhibitors (ICIs) have changed the oncology landscape in diseases such as melanoma, lung cancer, kidney cancer, and many others. Instead of directly destroying malignant cells, these drugs act like keys that unlock the barriers restricting T lymphocytes, allowing them to recognize and eliminate the tumor. However, by removing these blockades, the barriers that normally prevent autoimmunity also disappear. As a result, a significant percentage of patients develop uncontrolled reactions known as immune-related adverse events (irAEs), which can affect everything from the skin and intestines to vital organs such as the heart or the nervous system.

To control these side effects, the most widely used tool is corticosteroids. These drugs have been part of medicine for decades thanks to their ability to rapidly reduce inflammation and regulate uncontrolled immune responses. The problem is that their function is, in some ways, the opposite of immunotherapy: while immunotherapy seeks to stimulate the defenses, steroids suppress them. This raises the key question that troubles both doctors and patients: to what extent can corticosteroids diminish the benefits of immunotherapy?

The answer is not uniform. Scientific evidence shows that the impact depends on when, how much, and why steroids are used. For example, when a patient receives corticosteroids before or at the very start of immunotherapy, especially in high doses, the chances of success are lower. This makes sense: if the immune system is suppressed at the very moment the treatment is trying to activate it, the antitumor effect may be limited. But here lies an important nuance: many times, these patients need steroids because their disease is already very advanced, with severe symptoms such as brain edema, pain, or respiratory distress. In other words, it is not always the drug that is to blame, but rather the aggressiveness of the underlying cancer.

On the other hand, when corticosteroids are used in low doses or for reasons not directly related to cancer—such as in patients with preexisting autoimmune diseases—the impact on the efficacy of immunotherapy seems minimal. The same is true if steroids are administered later on, once immunotherapy has had time to awaken an effective immune response: in those cases, the potential damage to treatment efficacy is much smaller.

The use of steroids to treat the very side effects of immunotherapy is another area of debate. On one hand, patients who develop immune-related toxicities often respond better to treatment, making these effects a kind of “marker” that the immune system is working intensely against the tumor. On the other hand, it is inevitable to resort to steroids when these reactions endanger the patient’s life or quality of life. The good news is that, in most cases, administering corticosteroids to control irAEs does not erase the benefits of immunotherapy, although it could slightly reduce them if used in very high doses or for long periods.

An additional challenge is that corticosteroids, when used long-term, carry their own side effects: they increase the risk of infections, cause metabolic alterations, muscle weakness, osteoporosis, insomnia, mood changes, and even ocular damage. For this reason, the scientific community is searching for steroid-sparing strategies. Among them are more specific drugs, such as antibodies directed against inflammatory molecules (IL-6, TNF-α) or modulators of immune signaling (JAK or BTK inhibitors). Even very targeted rescue therapies, such as abatacept, have been tested to control severe complications without completely shutting down the antitumor response. Although these options are still in the research phase, they represent the hope for a more precise and less toxic approach in the future.

Figure 1. Immunotherapy boosts the immune system to attack tumors, while corticosteroids suppress immune activity to control side effects—highlighting the delicate balance between efficacy and safety.

Ultimately, the use of corticosteroids in immunotherapy is a delicate balancing act. It is not about banning them or fearing them, since they remain the best tool for managing severe complications. Rather, it is about learning to use them strategically: at the right dose, at the right time, and always evaluating the clinical context of each patient. Immunotherapy has taught us that the immune system is a powerful ally against cancer, but also that it requires discipline and control. Corticosteroids are, for now, an inevitable part of that control, while science advances toward more specific therapies that may preserve antitumor efficacy to the fullest without compromising patient safety.

Main Reference: 

Goodman, R. S., Johnson, D. B., & Balko, J. M. (2023). Corticosteroids and Cancer Immunotherapy. Clinical cancer research : an official journal of the American Association for Cancer Research, 29(14), 2580–2587. https://doi.org/10.1158/1078-0432.CCR-22-3181

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