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

Abstract

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-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.