Abstract
Simple SummaryOesophageal cancer rates are increasing rapidly with patients often presenting at an advanced stage. The current approach to treatment involves radiotherapy, chemotherapy, or combination chemoradiotherapy with surgery; however, only a fraction of these patients will achieve meaningful responses. Therefore, there is a need to better understand the tumour and lymph node microenvironments to inform future treatment strategies. This study measured immune markers including immune checkpoint expression in tumour and lymph node tissue in oesophageal cancer patients and patient clinical outcomes, including survival time, response to treatment, and adverse events. We report herein that nodal metastases is of equal prognostic importance to clinical tumour stage and tumour regression grade in OAC and we observed a more immunosuppressive microenvironment in the tumour compared with the lymph node.Response rates to the current gold standards of care for treating oesophageal adenocarcinoma (OAC) remain modest with 15–25% of patients achieving meaningful pathological responses, highlighting the need for novel therapeutic strategies. This study consists of immune, angiogenic, and inflammatory profiling of the tumour microenvironment (TME) and lymph node microenvironment (LNME) in OAC. The prognostic value of nodal involvement and clinicopathological features was compared using a retrospective cohort of OAC patients (n = 702). The expression of inhibitory immune checkpoints by T cells infiltrating tumour-draining lymph nodes (TDLNs) and tumour tissue post-chemo(radio)therapy at surgical resection was assessed by flow cytometry. Nodal metastases is of equal prognostic importance to clinical tumour stage and tumour regression grade (TRG) in OAC. The TME exhibited a greater immuno-suppressive phenotype than the LNME. Our data suggests that blockade of these checkpoints may have a therapeutic rationale for boosting response rates in OAC.
Highlights
Introduction conditions of the Creative CommonsMultimodal neoadjuvant therapy consisting of chemotherapy or chemoradiotherapy has become the standard-of-care for stage II–III cancer of the oesophagus and the oesophagogastric junction (OGJ)
The downgrading of nodal status following neoadjuvant treatment positively correlates with survival [17], in patients that do not display a local response in their primary tumour [15]
Adverse features consisted of poor differentiation, perineural, lymphatic, and vascular invasion, with a novel three-grouping stratification of 0, 1–2, and 3–4 adverse features previously described by our department [34]
Summary
Introduction conditions of the Creative CommonsMultimodal neoadjuvant therapy consisting of chemotherapy or chemoradiotherapy has become the standard-of-care for stage II–III cancer of the oesophagus and the oesophagogastric junction (OGJ). The potential benefits of neoadjuvant therapy include. Neoadjuvant treatment results in a complete pathological response in just 15–30% of patients, and it is this subgroup that gains the survival benefit from systemic therapy [2,3]. Curative surgery includes lymph node dissection and [7] pathological staging of resected nodes (ypN) has been shown to independently predict survival for oesophageal cancer patients [8,9,10,11,12]. The downgrading of nodal status following neoadjuvant treatment (where ypN is less than cN) positively correlates with survival [17], in patients that do not display a local response in their primary tumour [15]. It has been reported that those with nodal downstaging have shorter median survival than node-negative patients before treatment [17,18]
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