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

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.