Stromal regulatory T-cells are associated with a favourable prognosis in gastric cancer of the cardia

Background: Recent evidence suggests that CD4(+)CD25(+)FoxP3(+) regulatory T-cells (Treg) may be responsible for the failure of host anti-tumour immunity by suppressing cytotoxic T-cells. We assessed the prognostic significance of tumour infiltrating lymphocytes (TIL) in intestinal-type gastric cardiac cancer. Methods: Tumour infiltrating lymphocyte (TIL) subsets and tumour infiltrating macrophages (TIM) were investigated in 52 cases using tissue microarrays. The interrelationship between the cell populations (CD3+, CD8+, CD20+, CD68+, GranzymeB+, FoxP3+) in different compartments and NED-survival was investigated (median follow-up time: 61 months). Results: Intraepithelial infiltration with TIL and TIM including Treg was generally low and not related to NED-survival. However, patients with large numbers of FoxP3+ Treg in the tumour stroma (>125.9 FoxP3(+)TILs/mm(2)) had a median survival time of 58 months while those with low FoxP3+ TIL counts (<125.9 FoxP3(+)TILs/mm(2)) had a median survival time of 32 months (p = 0.006). Patients with high versus low stromal CD68(+)/FoxP3(+) cell ratios in primary tumour displayed median survivals of 32 and 55 months, respectively (p = 0.008). Conclusion: Our results suggest that inflammatory processes within the tumour stroma of gastric intestinal-type adenocarcinomas located at the gastric cardia may affect outcome in two ways. Tumour-infiltrating macrophages are likely to promote carcinogenesis while large numbers of Treg are associated with improved outcome probably by inhibiting local inflammatory processes promoting carcinogenesis. Thus, inhibition of Treg may not be a feasible treatment option in gastric adenocarcinoma.