Selective infiltration of CCR5+CXCR3+ T lymphocytes in human colorectal carcinoma

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Abstract
T cell infiltration in colorectal cancer is associated with a favorable prognosis, suggesting an occurrence of a certain degree of anti‐tumor immunity. T helper type 1 (Th1) and Th2 cells are now known to selectively express CC‐chemokine receptor 5 (CCR5)/CXC‐chemokine receptor 3 (CXCR3) and CCR4, respectively. To clarify the mechanism of T cell infiltration, we examined in situ expression of these chemokine receptors and their respective chemokine ligands in 40 cases of human colorectal cancer. Immunohistochemistry showed a predominant accumulation of T cells expressing CCR5 and CXCR3 mainly along the invasive margin, whereas those expressing CCR4 were rare. Flow cytometric analysis showed that more than half of CD8+ T cells and a fraction of CD4+ cells isolated from fresh tumor tissues co‐expressed CCR5 and CXCR3, and CD8+ T cells and CD4+ cells predominantly produced interferon‐γ (IFN‐γ) over interleukin‐4 (IL‐4) after in vitro stimulation. RANTES/CCL5, a ligand of CCR5, was localized within infiltrating CD8+ T cells in a granular pattern, whereas IP‐10/CXCL10, a ligand of CXCR3, was localized in cancer cells and macrophages along the invasive margin. These data were consistent with an active recruitment of T cells expressing CCR5 or CXCR3 into the invasive margin of colorectal cancer. With the previous clinicopathological studies showing a favorable prognostic impact of T cell infiltration in colorectal cancer, our study supports the occurrence of a certain level of Th1‐shifted cellular immune responses in human colorectal cancer.