Heme-oxygenase-1 (HO-1) as a potential biomarker for ICIs in patients with advanced lung cancer

BackgroundImmune checkpoint inhibitors (ICIs) have significantly improved the outcome in patients with lung cancer. However, heterogeneity in clinical benefit and absence of a reliable biomarker still represent an unmet need. We evaluated the role of heme-ossigenase-1 (HO-1) expression on monocytes in resistance to ICI.Methods“ImmunoEGA� is a prospective, observational study in patients with advanced tumors, treated with ICIs at the ‘Maggiore della Carità’ Hospital in Novara, IT. Overall, 122 patients affected by lung cancer have been recruited from 2018 to 2023. In the present study we used cytofluorimetry to analyse monocytes subpopulations and HO-1 expression on their surface, on blood samples collected at baseline, before start of treatment and at the time of disease progression (34 patients). The primary endpoint was treatment outcome in terms of progression free (PFS) and/or overall survival (OS).ResultsAt baseline, the frequency of classical monocytes was higher as compared to non-classical and intermediate subgroups, independently from type and duration of response (mean percentage: 48,4% vs 7,8 vs 23,9%; p<0.0001). A significant correlation between higher frequency of classical monocyte at baseline and PFS was observed (14.0 vs 6.5 mos, p= 0,0171), as well as a relative increase in the frequency of classical monocytes at the time of disease progression (PD) (p=0,0554). No differences were detectable in HO-1 expression across monocytes subtypes at baseline. Patients with lower HO-1 expression on classical and intermediate monocytes had an improved PFS (15,5 vs 6,5 mos p=0,0057), as well as an improved OS (18 vs 11.5 m, p=0.0378).ConclusionsIn patients with lung cancer treated with ICI a higher frequency of classical monocytes is predictive of an improved outcome. Lower HO-1 expression on intermediate and classical monocytes correlates with an improved outcome. Conversely, the expression of HO-1 in classical and intermediate monocytes increases at PD, suggesting its implication in promoting cancer progression. These data suggest that the level of HO-1 expression might be used as a potential biomarker of ICIs benefit. Additional data will be presented.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureAll authors have declared no conflicts of interest.