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High-Dose Steroids Undermine Checkpoint Inhibitors in Non-Small Cell Lung Cancer

A new study combining retrospective patient data with a preclinical mouse model reveals high-dose corticosteroids undermine checkpoint inhibitor benefits by halting T-cell maturation, blocking circulating biomarkers, leading experts to call for revised treatment guidelines.

Overview

  • Retrospective analysis of 277 Stage II–IV NSCLC patients across three centers found that high-dose corticosteroids given before or during checkpoint inhibitor therapy were linked to reduced tumor shrinkage and shorter survival.
  • After adjusting for disease stage and progression, steroid use emerged as the strongest independent predictor of immunotherapy failure in the study cohort.
  • A mechanistic mouse model confirmed that corticosteroids inhibit T-cell maturation in real time, weakening the immune attack against cancer cells.
  • Researchers discovered that steroids block key circulating biomarkers used to monitor disease progression, potentially delaying treatment adjustments and reducing therapy effectiveness.
  • Findings have prompted oncologists to advocate for updated clinical guidelines that balance necessary symptom relief with the preservation of immunotherapy efficacy.