FOXP3 is a favourable prognostic indicator in oesophageal adenocarcinoma

Oesophageal Adenocarcinoma (OAC) is a cancer with poor prognosis although multimodal treatment has greatly improved clinical outcomes for certain patients. However, currently, there is no way to predict which patients will benefit from neoadjuvant regimens. The level of immune cell tumour infiltration has shown prognostic ability in other cancer types. This study aimed to define the immune landscape of OAC tumours and describe interactions with clinicopathological parameters.

Three micron sections from n = 135 treatment-naïve OAC biopsies were stained using multiplex immunofluorescence for immune markers CD8, CD3, FOXP3, HLA-DR, CD68 and CD163. Expression of the immune markers in the tumour and stroma compartments and other pathological markers such as tumour buds (TB), poorly differentiated clusters (PDCs) and the tumour stroma ratio (TSR) were quantified by digital pathology software and the ability of each marker to predict patient clinical outcomes was investigated.

On log-rank analysis stromal expression of FOXP3, CD68 and CD163 and tumour expression of FOXP3 and CD163 were all associated with improved OS (Log-rank p = 0.003, p = 0.0009, p = 0.003, p = 0.015, p = 0.039). PDCs were associated with worse OS (p = 0.039). Multivariate analysis identified tumour expression of FOXP3 as an independent favourable prognostic factor for OS (HR = 0.398, 95 % CI: 0.178-0.887, p = 0.024).

Stromal expression of CD68, CD163 and FOXP3 and tumour expression of FOXP3 and CD163 were associated with improved outcome while the presence of PDCs was associated with worse outcome. FOXP3 was found to be an independent favourable prognostic factor, highlighting the need to better understand the role of FOXP3 in OAC.