Background Oesophageal adenocarcinoma (OAC) is increasingly common in the west, and survival remains poor at 10–15 % at 5 years. Immune responses are increasingly implicated as a determining factor of tumour progression. The ability of lymphocytes to recognise tumour antigens provides a mechanism for a host immune attack against cancer providing a potential treatment strategy.Materials and MethodsTumour infiltrating lymphocytes (TILs: CD3+, CD4+, CD8+ and FOXp3+) were assessed by immunohistochemistry using tissue microarrays in a contemporary and homogeneous cohort of OAC patients (n = 128) undergoing curative treatment.Results Multivariate analysis identified three independent prognostic factors for improved cancer-specific survival (CSS): increased CD8+ TILs (p = 0.003), completeness of resection (p < 0.0001) and lower pathological N stage (p < 0.0001). Independent prognostic factors for favourable disease-free survival included surgery-only treatment (p = 0.015), completeness of resection (p = 0.001), increased CD8+ TILs (p < 0.0001) and reduced pathological N stage (p < 0.0001). Higher levels of TILs in the pathological specimen were associated with significant pathological response to neoadjuvant chemotherapy (NAC). On multivariate analysis increased levels of CD4+ (p = 0.017) and CD8+ TILs (p = 0.005) were associated with significant local tumour regression and lymph node downstaging, respectively.DiscussionOur results establish an association of TILs and survival in OAC, as seen in other solid tumours, and identify particular TIL subsets that are present at higher levels in patients who responded to NAC compared to non-responders. These findings highlight potential therapeutic strategies in EAC based on utilising the host immunological response and highlight the immune responses biomarker potential.Electronic supplementary materialThe online version of this article (doi:10.1007/s00262-016-1826-5) contains supplementary material, which is available to authorized users.

Background:Oesophageal adenocarcinoma (OAC) is one of the fastest rising malignancies with continued poor prognosis. Many studies have proposed novel biomarkers but, to date, no immunohistochemical markers of survival after oesophageal resection have entered clinical practice. Here, we systematically review and meta-analyse the published literature, to identify potential biomarkers.Methods:Relevant articles were identified via Ovid medline 1946–2013. For inclusion, studies had to conform to REporting recommendations for tumor MARKer (REMARK) prognostic study criteria. The primary end-point was a pooled hazard ratio (HR) and variance, summarising the effect of marker expression on prognosis.Results:A total of 3059 articles were identified. After exclusion of irrelevant titles and abstracts, 214 articles were reviewed in full. Nine molecules had been examined in more than one study (CD3, CD8, COX-2, EGFR, HER2, Ki67, LgR5, p53 and VEGF) and were meta-analysed. Markers with largest survival effects were COX-2 (HR=2.47, confidence interval (CI)=1.15–3.79), CD3 (HR=0.51, 95% CI=0.32–0.70), CD8 (HR=0.55, CI=0.31–0.80) and EGFR (HR=1.65, 95% CI=1.14–2.16).Discussion:Current methods have not delivered clinically useful molecular prognostic biomarkers in OAC. We have highlighted the paucity of good-quality robust studies in this field. A genome-to-protein approach would be better suited for the development and subsequent validation of biomarkers. Large collaborative projects with standardised methodology will be required to generate clinically useful biomarkers.

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