Steroid-induced modulation of the tumor immune microenvironment: Implications for cancer progression and...

Glucocorticoids (GCs) remain indispensable in oncology due to their strong anti-inflammatory, anti-oedema, and immunosuppressive effects, which are crucial for controlling cancer symptoms and treatment-related toxicities. However, the expanding use of immunotherapies, particularly immune checkpoint blockade and CAR-T cell approaches, has highlighted the paradoxical influence of steroids on anti-tumor immunity. GCs profoundly reshape the tumor immune microenvironment (TIME) by suppressing cytotoxic T-cell activity, enhancing regulatory T cells, polarizing macrophages toward tumor-promoting states, inhibiting NK and dendritic cell function, and expanding myeloid-derived suppressor cells. Together, these alterations weaken immune surveillance and may promote tumor progression, metastasis, and therapeutic resistance. Both systemic and tumor-derived GC signaling further interact with niches that sustain cancer stemness. Clinical data indicate that the timing, dose, and duration of steroid exposure are decisive, with early or high-dose administration frequently associated with poorer immunotherapy outcomes. Therefore, clarifying GC-driven immune modulation is critical to balance toxicity control while preserving anti-tumor efficacy in precision immunotherapy.