P1.107. Macrophage Infiltration and FoxP3 Density Predict Treatment Response and Survival in Esophageal Cancer Patients
Esophageal Cancer: Molecular Biology/Pathology The tumor microenvironment (TME) holds an important role in the biological behaviour of the esophageal cancer, influenced by neoadjuvant treatment (NAT). However, its correlation to patient outcomes remains poorly defined. The aim of this study was to assess the prognostic value of TME in terms of long-term recurrence and survival. All eligible patients with esophageal adenocarcinoma (EAC) and squamous cell carcinoma (SCC), treated with curative intent including surgery between 01.2009 and 12.2021, were retrospectively analyzed. Immunohistochemical analysis of pre-treatment biopsies and surgical specimens, was performed for biomarkers CD3, CD8, CD68, CD163, Treg/FoxP3 and PD-L1 (combined positive score, CPS). Histologic slides were scanned at high resolution (x400), and the above biomarkers were eye-counted as mean number/high power field. Pathological response to NAT was assessed with the Mandard tumor regression grade (TRG). The chi2 and Fisher tests were used to compare categorical, and the student’s t test continuous variables. Overall survival (OS) and disease-free survival (DFS) were analyzed using Cox simple and multiple regression. Overall, 64 patients were included (51 EAC, 13 SCC) in the present study; 81% of patients were male, with a median age of 64 years (IQR 57-69), and a median follow-up of 48 months. Although baseline TME composition was comparable in all patients, poor pathological responders (TRG 3-5) showed higher macrophage infiltration after NAT compared to good responders (TRG 1-2) (Mean total macrophages [CD68+] 63.6 poor vs 44.3 good responders, p = 0.002, mean M2-like [CD163+] 50.3 poor vs 38.3 good responders, p = 0.038). In multivariable analysis, Treg/FoxP3 expression (HR 0.95, 95% CI 0.90–1.00, p = 0.041) and pathological nodal status (HR 2.37, 95% CI 1.58–3.54, p < 0.001) remained independent predictors of DFS, but not OS. Within the EAC subgroup, FOXP3 expression was associated with more favourable OS (adjHR 0.93, 95% CI0.88–0.98, p = 0.008) and DFS (adjHR 0.95, 95% CI 0.90–1.00, p = 0.049). The present study indicates increased macrophage concentration (total and M2-like phenotype) to be related to poor response to NAT. In addition, increased numbers of Treg/FOXP3 lymphocytes were associated with a more favourable overall and disease-free patient survival especially within the adenocarcinoma histology. Targeted agents with inhibitory action towards macrophages and expansive action for Treg/FOXP3 lymphocytes might have therapeutic potential for esophageal cancer patients.