In non-small cell lung cancer (NSCLC), immune checkpoint inhibitors (ICIs), especially anti-PD-1/PD-L1 treatments, have significantly improved treatment outcomes. It is unknown how steroids affect blood-based biomarkers such as CX3CR1+CD8+ T cells and neutrophil-to-lymphocyte ratio (NLR), which are still under investigation. Researchers examined the clinical results of 277 NSCLC patients who received ICI therapy at two academic institutions in this study between October 2013 and August 2023.
Mice with MC38 tumors, a bedside-to-bench method used to find concomitant steroids, inhibited the rise of CX3CR1+CD8+ T cells and reduced the antitumor efficacy of anti-PD-1 therapy. The use of steroids to manage immune-related adverse events (irAEs) from ICI therapy is well-established, and it does not appear to compromise the overall clinical benefits of the treatment.
Treatment was given at the University of Southern California (USC) for 189 patients and Roswell Park Comprehensive Cancer Center (RPCCC) for 88 patients. The RPCCC Institutional Review Board (I 188310) or USC Institutional Review Board (HS-15-00200) approved this study, and it was carried out in compliance with the Declaration of Helsinki. The immune-related RECIST at 6 to 12 weeks was used to determine the best clinical response to immunotherapy or chemo-immunotherapy.
Patients who had either obtained a full or partial reaction were considered responders, while patients with either progressing or stable illness were considered non-responders. At RPCCC, blood samples were collected prior to treatment and at the time of standard-of-care blood draws every three to six weeks for a total of 12 weeks. The cells were regularly checked for mycoplasma using PCR and kept at 37°C in a humidified environment with 5% CO2.
The mean and range for continuous variables and relative frequencies for categorical variables were used to gather and report patient demographic and clinical data. Overall survival (OS) and progression-free survival (PFS) were calculated by using the Kaplan–Meier technique. This model was used to calculate hazard ratios (HRs) and their associated 95% confidence interval (CI). Variables with P < 0.05 in univariate analysis were subjected to further multivariate analysis.
NLR was determined at the start of ICI therapy by dividing the absolute neutrophil count by the absolute lymphocyte count. At RPCCC, patients receiving steroids showed a high chance of RT (P = 0.0021) and brain metastases (P = 0.0001). At USC, patients on steroids were more likely to receive chemo-immunotherapy than immunotherapy alone (P = 0.0034). Approximately 29 out of the 77 patients at RPCCC who were not receiving steroids when they started ICI therapy were considered responders, while the remaining 48 were considered non-responders. At USC, of the 179 patients not on steroids, 80 were responders and 99 were non-responders.
In this study, the results suggest that nine patients at USC and four patients at RPCCC discontinued using corticosteroids during one to 30 days prior to beginning ICI therapy. The response rate was higher for patients who stopped using steroids prior to the start of ICI therapy compared to those who remained on ICI medication. The findings suggest that reducing or discontinuing steroids before initiating ICI therapy may enhance treatment efficacy and immune surveillance.
Reference: 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. Cancer Res Commun. 2025;5(7):1082–1094. doi:10.1158/2767-9764.CRC-25-0051
