Steroids May Hinder Immunotherapy Effectiveness in Non-Small Cell Lung Cancer

Study Highlights Detrimental Impact of Baseline Steroid Use on Treatment Outcomes

A recent study published in Common Cancer Research reveals a notable link between baseline steroid use and reduced efficacy of immunotherapy – specifically immune checkpoint inhibitors (ICIs) – in patients with non-small cell lung cancer (NSCLC). Researchers at Keck Medicine of the University of Southern California (USC) found that steroids appear to suppress the body’s natural cancer-fighting T-cells, potentially leading to worse outcomes despite treatment.

Key Findings: Steroids and the Immune Response

The research team investigated the impact of glucocorticoids, commonly used to manage symptoms associated with lung cancer, on the effectiveness of ICI therapy. Their analysis demonstrated that a baseline peripheral blood neutrophil-to-lymphocyte ratio (NLR) below 5 was a strong indicator of positive prognosis unless the patient was concurrently receiving steroids.In steroid-treated patients, this prognostic value disappeared.

Further examination revealed a noticeably lower baseline frequency of circulating CX3CR1+CD8+ T cells – a type of immune cell crucial for antitumor activity – in patients taking steroids. Using both patient data and mouse models with MC38 tumors, the researchers confirmed that concurrent steroid use significantly decreased the antitumor efficacy of anti-PD-1 therapy. Importantly, discontinuing steroids at the initiation of immunotherapy did not negatively impact survival.

“Steroids where the biggest predictor of why certain immunotherapies may not be effective, even when considering multiple other factors such as stage and progression of the disease,” explained Dr. Fumito ito, lead author of the study and an oncologist and immunologist at Keck Medicine. “Our findings reveal that steroids stop the body’s natural cancer-fighting cells, T-cells, from maturing. This makes them unable to attack the cancer as vigorously as they usually would, leading to worse outcomes for patients.”

Implications for Clinical Practice & Biomarker Interpretation

The study underscores the importance of carefully considering steroid use in patients undergoing ICI therapy for NSCLC.The authors caution that the findings suggest immune-related biomarkers assessed in patients on steroids should be interpreted with caution, as steroid use can alter these markers and potentially misguide treatment decisions.

Dr. ito emphasizes the need for individualized treatment plans. “Without the presence of circulating biomarkers to inform our decisions, oncologists cannot treat the cancer as effectively, and patients may miss out on the best treatment for their cancer,” he stated. “We certainly know that steroids will continue to play an vital role in lung cancer care, but it is indeed critically important to understand their potential limitations. Each patient should talk to their oncologist to make sure they have the best possible care plan tailored to their specific needs.”

The research team hopes these findings will empower oncologists and healthcare providers to make more informed decisions, ultimately improving outcomes for patients with NSCLC. While steroids remain a valuable tool for symptom management, a thorough discussion of their potential impact on immunotherapy effectiveness is now crucial.

REFERENCES

1. Polyakov L, Lim A, Meyer A, et al. Impact of Glucocorticoids on Immune Checkpoint Inhibitor Efficacy and Circulating Biomarkers in non-Small Cell Lung Cancer Patients. Common cancer res.2025; 5 (7): 1082-1094. DOI: 10.1158/2767-9764.CRC-25-0051
2. University of Southern California – Health Sciences. Common medication for lung cancer symptoms found to limit effectiveness of cancer treatment. News release. July 7, 2025. Accessed July 7, 2025. https://www.eurekalert.org/news-releases/1089842