Prognostic Interplay between Tumor-Infiltrating T and B Lymphocytes in Esophageal and Gastric Adenocarcinoma
Maria C Svensson1*, Richard Fristedt1, Charlotta Hedner1, David Borg1, Agnieszka Krzyzanowska2, Anders Bjartell2, Jakob Eberhard1, Björn Nodin1, Karin Leandersson3, Karin Jirström1
1Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Lund, Sweden; 2Center for Molecular Pathology, Department of Translational Medicine, Lund University, Malmö, Sweden; 3Cancer Immunology, Department of Translational Medicine, Lund University, Malmö, Sweden
Several studies have demonstrated a beneficial prognostic impact of tumor-infiltrating T lymphocytes in esophageal and gastric adenocarcinoma, but whether infiltrating B lymphocytes also have a prognostic impact has not yet been reported. Immunohistochemistry and automated image analysis was applied to assess the density of T lymphocytes (CD3+, CD8+, FoxP3+) and B lymphocytes (CD20+) in radiochemo-naïve tumors from a consecutive cohort of 174 patients with resected esophageal or gastric adenocarcinoma. Cox proportional hazard’s modelling was applied to examine the impact of the investigated markers on overall survival (OS) using the median number as cutoff. High infiltration of CD3+, CD8+, and FoxP3+ lymphocytes was associated with a significantly prolonged OS, however only in tumors with high B lymphocyte infiltration. In tumors with low B cell infiltration, there was a non-significant trend towards a reduced OS for patients with CD3+ and CD8+ high tumors. A significant prognostic interaction was found between CD20+ and CD3+ lymphocytes as well as CD20 + and CD8+ lymphocytes (p for interaction = 0.017 and 0.033, respectively), but not between CD20+ and FoxP3+ lymphocytes. These results demonstrate that the prognostic value of infiltrating T lymphocytes in esophageal and gastric adenocarcinoma, in particular CD8+ cytotoxic T lymphocytes, depends on the presence of B lymphocytes. Collectively, these data support that the antitumor effects of tumor infiltrating T lymphocytes might be dependent on a contribution from B lymphocytes in order to function efficiently and influence clinical outcome.
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