Journal
ONCOTARGET
Volume 8, Issue 42, Pages 72108-72126Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.19437
Keywords
T lymphocytes; B lymphocytes; esophageal cancer; gastric cancer; prognosis
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Funding
- Swedish Cancer Society
- Swedish Research Council
- Mrs. Berta Kamprad Foundation
- Swedish Government Grant for Clinical Research (ALF)
- Lund University Faculty of Medicine
- Lund University Hospital Research Grants
- Lions Cancerfond
- Erik, Karin and Gosta Selanders Foundation
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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 (p(interaction) = 0.012, 0.009 and 0.007, respectively) and for FoxP3(+) with IGKC(+) cells (p(interaction) = 0.034). In esophageal tumors, there was only a significant interaction for CD3(+) and CD20 (+) cells (p(interaction) = 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-naive 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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