Research Papers:

The integrative clinical impact of tumor-infiltrating T lymphocytes and NK cells in relation to B lymphocyte and plasma cell density in esophageal and gastric adenocarcinoma

Maria C. Svensson _, Carl Fredrik Warfvinge, Richard Fristedt, Charlotta Hedner, David Borg, Jakob Eberhard, Patrick Micke, Björn Nodin, Karin Leandersson and Karin Jirström

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Oncotarget. 2017; 8:72108-72126. https://doi.org/10.18632/oncotarget.19437

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Maria C. Svensson1, Carl Fredrik Warfvinge1, Richard Fristedt1, Charlotta Hedner1, David Borg1, Jakob Eberhard1, Patrick Micke2, Björn Nodin1, Karin Leandersson3 and Karin Jirström1

1Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Lund, Sweden

2Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Uppsala, Sweden

3Cancer Immunology, Department of Translational Medicine, Lund University, Malmö, Sweden

Correspondence to:

Maria C. Svensson, email: [email protected]

Keywords: T lymphocytes, B lymphocytes, esophageal cancer, gastric cancer, prognosis

Received: February 24, 2017     Accepted: June 20, 2017     Published: July 21, 2017


Background: Several studies have demonstrated a prognostic impact of tumor-infiltrating T lymphocytes and natural killer (NK) cells in esophageal and gastric adenocarcinoma, but whether these associations differ by the density of tumor-infiltrating immune cells of the B cell lineage remains largely unknown.

Results: High infiltration of any T and NK lymphocytes investigated was in general associated with a favorable prognosis, but the strongest beneficial prognostic impact was seen in combination with high B lymphocyte infiltration. These findings were most evident in gastric cancer, where significant interactions in relation to OS were observed for CD3+, CD8+ and FoxP3+ with CD20+ cells (pinteraction =0.012, 0.009 and 0.007, respectively) and for FoxP3+ with IGKC+ cells (pinteraction =0.034). In esophageal tumors, there was only a significant interaction for CD3+ and CD20 + cells (pinteraction =0.028).

Methods: Immunohistochemistry and automated image analysis was applied to assess the density of T lymphocytes (CD3+, CD8+, FoxP3+) and NK cells (NKp46+) in chemoradiotherapy-naïve tumors from a consecutive cohort of 174 patients with resected esophageal or gastric adenocarcinoma. The density of B lymphocytes (CD20+) and plasma cells (IGKC+) had been assessed previously. Kaplan-Meier analysis and Cox proportional hazard’s modelling was applied to examine the impact of the investigated markers on time to recurrence (TTR) and overall survival (OS).

Conclusions: These data support that the antitumoral effects of tumor-infiltrating T lymphocytes in esophageal and gastric adenocarcinoma may be largely dependent on a functional interplay between T and B lymphocytes or plasma cells.

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