594. THE IMPACT OF PATIENT CHARACTERISTICS AND NEOADJUVANT TREATMENT ON THE TUMOUR MICRO-ENVIRONMENT OF ESOPHAGEAL CANCER

Abstract Background Esophageal cancer remains associated with poor prognosis, as even with the current standards of multimodal treatment and oncologic surgery many patients show no response to treatment, or suffer early recurrence after surgery. In the current era of precision medicine, a better understanding of the tumor microenvironment (TME) is needed to identify patients with unfavourable biology, but also to illustrate the physiopathology of host reaction to treatment. The aim of this monocentric translational study was to analyse the biomolecular characteristics of esophageal cancer in relation to key clinicopathologic parameters, and in particular to the response to neoadjuvant treatment. Methods A series of patients operated for esophageal cancer with curative intent between 01.2009 and 12.2021 were included in this study. Clinicopathological data were collected, and initial biopsies and surgical specimens were reassessed by a senior GI pathologist. The immune infiltrate markers CD3, CD8, CD163, CD68, PDL1and FOXP3 were recorded as cell counts/high power field. The CPS score was used for PD-L1 quantification, whereas the Mandard regression grade (TRG) assessed pathologic response to neoadjuvant treatment (NAT). Continuous variables were compared with the Mann-Whitney-U and ANOVA tests, and categorical ones with the Chi-2 test. Significance threshold was set at p<0.05. Results Overall, 68 patients (82.4% males, mean age 62.4□9.4 years, 79.4% adenocarcinoma) were included. TME in smokers had lower M2-like (CD163+, p=0.009) and total macrophages (CD68+, p=0.001), but similar CD163/68 ratio and T-cells as non-smokers. Adenocarcinoma histology compared to squamous cell, showed higher M2-like macrophages (p=0.023), mean CPS score (p=0.038) and T-cell infiltration (p=0.006). NAT increased macrophages and cytotoxic T-cells, and decreased Treg/FoxP3 cells in the TME. Chemotherapy, compared to chemoradiation, was associated with higher T-cell TME infiltration. Good responders to NAT (TRG1-2) had similar initial TME characteristics as poor responders, but they displayed lower macrophage count upon final histology (p=0.003). Conclusions In the present series, active smoking was related to attenuated, whereas adenocarcinoma histology to enhanced M2-like macrophage infiltration of esophageal cancer TME. Neoadjuvant treatment, and especially chemotherapy, recruited macrophages and T-cells in the TME. None of the biomarkers derived from the initial biopsies were associated with response to NAT, although an increased macrophage count upon final histology was related to poor response. The present study provides valuable insight to the TME composition of esophageal cancer. However, further studies are needed to assess the exact functional role of TME elements, and specifically macrophages, and their impact on clinical outcomes.