Morphometric analysis of the balance between CXCR3⁺ T cells and FOXP3⁺ regulatory T cells in lymphocyte-rich and conventional gastric cancers

Lymphocyte-rich gastric carcinomas (Ly-rich GCs) are characterized by the formation of lymphoid stroma. Our previous study has shown abundant infiltration of CXCR3⁺ T cells and their frequent clustering with CXCL9 (monokine induced by interferon-γ)-expressing stromal cells in the lymphoid stroma of Ly-rich GCs. Foxp3⁺ regulatory T cells (Tregs) suppress immune responses in the peripheral tissues and play a role in the immunosuppression of cancer tissues. The present study was therefore undertaken to evaluate the significance of the balance between CXCR3⁺ T cells and Tregs in 44 Ly-rich and 37 conventional GCs by morphometrical analyses of immunohistochemistry. Compared with the pronounced infiltration of CXCR3⁺ T cells in the lymphoid stroma, the numbers of Foxp3⁺ cells were relatively low in Ly-rich GCs. Therefore, the ratios of CXCR3⁺/Foxp3⁺ cells were much higher in Ly-rich GCs than in conventional GCs. This suggests the occurrence of T-helper type 1 (Th1)-shifted immune responses in Ly-rich GCs. On the other hand, conventional GCs were characterized by a paucity of CXCR3⁺ T cells and a relative abundance of Tregs. Furthermore, the stroma inside the cancer was characterized by even less CXCR3⁺ cells, suggesting a strongly immunosuppressive microenvironment. Since Tregs are known to express CCR4, we also examined the tissue distribution of cells expressing its ligand CCL22. CCL22 was not detected in conventional GCs and only sparsely detected in dendritic cells but not in cancer cells in Ly-rich GCs. To conclude, Tregs may play a more important role in conventional GCs than in Ly-rich GCs from the viewpoint of immunosuppression.