Tumour infiltrating lymphocytes correlate with improved survival in patients with oesophageal adenocarcinoma

Noble, Fergus, Mellows, Toby, McCormick Matthews, Leo H., Bateman, Adrian, Harris, Scott, Underwood, Tim, Byrne, James P., Bailey, Ian S., Sharland, Donna M., Kelly, Jamie J., Primrose, John N., Sahota, Surinder S., Bateman, Andrew R., Thomas, Gareth J and Ottensmeier, Christian H. (2016) Tumour infiltrating lymphocytes correlate with improved survival in patients with oesophageal adenocarcinoma. Cancer Immunology Immunotherapy, 65 (6), 651-662. (doi:10.1007/s00262-016-1826-5). (PMID:27020682)

Abstract

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 methods: Tumour 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.
Discussion: Our 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.

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Contributors

Author: Tim Underwood

Author: John N. Primrose

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