Corticosteroids and Cancer Immunotherapy

Abstract

Despite revolutionizing cancer management, immunotherapies dysregulate the immune system, leading to immune-mediated adverse events. These common and potentially dangerous toxicities are often treated with corticosteroids, which are among the most prescribed drugs in oncology for a wide range of cancer and noncancer indications. While steroids exert several mechanisms to reduce immune activity, immunotherapies, such as immune checkpoint inhibitors (ICI), are designed to enhance the immune system's inherent antitumor activity. Because ICI requires an intact and robust immune response, the immunosuppressive properties of steroids have led to a widespread concern that they may interfere with antitumor responses. However, the existing data of the effect of systemic steroids on immunotherapy efficacy remain somewhat conflicted and unclear. To inform clinical decision-making and improve outcomes, we review the impact of steroids on antitumor immunity, recent advances in the knowledge of their impact on ICI efficacy in unique populations and settings, associated precautions, and steroid-sparing treatment approaches.

Figure 1.

The Effects of Immunotherapy vs Corticosteroids on Immunity (A) Tumor antigens are presented to T cells by antigen-presenting cells (APCs) via major histocompatibility complex (MHC) and T cell receptors. Several co-receptors act as negative modulators of the immune responses at different molecular checkpoints. Activated T cells upregulate PD-1, and inflammatory signals in the tumor microenvironment upregulate PD-L1, which inhibits effector T cell activity. CTLA-4 binds to CD80 leading to T cell inactivation. Tumors minimize antitumor immunity by exploiting PD-1/PD-L1 and CTLA-4 checkpoint pathways. (B) Monoclonal antibodies that block either CTLA-4 or PD1/PD-L1 pathways increase the activity of tumor-reactive T cells. While this immune checkpoint inhibition restores the antitumor immune response, it also leads to autoimmunity (immune-related adverse events). (C) ICIs and corticosteroids produce antagonistic effects on the immune system. This suggests that steroids may mechanistically undermine ICI efficacy by suppressing necessary anti-tumor immune functions. This figure contains elements from Canva Pro.

Figure 2.

Factors that Influence Immunotherapy Efficacy While timing and dose are important considerations when prescribing steroids for patients on immunotherapy, it is also important to consider the indication for steroid use.