Abstract 1777P
Background
Immune checkpoint inhibitors (ICIs) have significantly improved the outcome of lung cancer patients; however, a significant proportion of patients fail to achieve a durable response. Aberrant immune cells have been detected in tumor microenvironment; in particular, tumor associated macrophages (TAMs), with high levels of hemeoxigenase-1 (HO-1+) seem to play a crucial defense mechanism through anti-oxidant, anti-inflammatory and anti-apoptotic properties. With these premises, we evaluated the prognostic role of HEME catabolism by the assessment of HO-1 expression level in monocytes subpopulations in peripheral blood samples of patients affected by advanced lung cancer (LC), candidate to ICIs.
Methods
Between 03/2020 and 03/2021 47 patients with advanced lung cancer were prospectively enrolled into this study; of these, 39 were eligible for HO-1 analysis in monocyte subpopulation. Peripheral Blood Mononuclear Cells (PBMCs) were collected at baseline and expression of HO-1 was assessed by Flow Cytometry analysis, in terms of Median Fluorescence Intensity (MFI), in three monocyte subpopulations: classical (CD14+/CD16-), non-classical (CD14-/CD16+) and intermediate (CD14+/CD16+). HO-1 levels were correlated with clinical outcome in terms of disease control rate at 6 months.
Results
Among 39 patients, 12 (34%) had a response duration <6 months. The expression of HO-1 in classical monocytes was significantly higher compared to intermediate and non-classical monocytes (Kruskal-Wallis test with Bonferroni’s correction p<0.0001). A Cox proportional hazard model showed that higher HO-1 levels in classical monocytes were associated with a trend for a lower risk of progression rate at 6 months (HR 0.60, 95%CI 0.18 – 2.07).
Conclusions
These preliminary results suggest that in lung cancer patients treated with ICIs higher levels of HO-1 in classical monocytes have a protective role and are associated with an improved outcome. Additional data on a larger patient set will be presented at the meeting.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
University of Eastern Piedmont.
Disclosure
All authors have declared no conflicts of interest.