Impact of stratifin/14-3-3σ on survival and interstitial lung disease in patients with non-small cell lung cancer receiving immune checkpoint inhibitors.

Background: Stratifin/14-3-3σ (SFN) is a new diagnostic biomarker of interstitial lung disease (ILD) with a diffuse alveolar damage (DAD) pattern as well as a predictor of resistance to anticancer therapy. Despite the potential clinical benefit of SFN, its impact on therapeutic efficacy of immune checkpoint inhibitors (ICIs) and ICI-induced interstitial lung disease (ICI-ILD) in patients with non-small cell lung cancer (NSCLC) receiving cancer immunotherapy is unknown.

Methods: Plasma samples were collected from patients with NSCLC at ICI initiation and 6 weeks later. The relationship between SFN levels and therapeutic efficacy of ICIs and development of ICI-ILD was analyzed.

Results: Pre-SFN levels were measured for 165 patients and post- and delta-SFN levels were measured for 113 patients. Of the patients with pre-SFN values, 25 developed ICI-ILD and 10 exhibited a DAD pattern. Among patients with post- and delta-SFN values, 15 developed ICI-ILD, and 6 had a DAD pattern. Pre- and post-SFN levels were not associated with ICI therapeutic efficacy or ICI-ILD. Meanwhile, delta-SFN, representing the change in SFN values between ICI initiation and at the 6-week point, was associated with progression-free survival, overall survival, disease control rate, and ICI-ILD image patterns.

Conclusion: SFN levels in plasma were associated with therapeutic efficacy and ICI-ILD pattern in patients with NSCLC receiving cancer immunotherapy. SFN can be a diagnostic biomarker for ICI-ILD with DAD patterns as well as a prognostic biomarker for cancer immunotherapy.