Functional CCR9 expression is associated with small intestinal metastasis.

In general, metastases to the small intestine are rare, and mostly occur in melanoma. CCR9 has been shown to be the principal chemokine receptor for the thymus expressed chemokine (TECK), a chemokine selectively expressed in the small intestine and thymus. Here we show that CCR9 is highly expressed on melanoma cells and all melanoma cell lines isolated from small intestinal metastases, and on a proportion of cell lines from other sites. Only melanoma cells and cell lines from small intestinal metastases, however, were responsive to the CCR9 ligand TECK, as assessed by receptor downregulation and by actin polymerization. CCR9 expression was also found on the adenocarcinoma cell line CaCo-2 expressing characteristics of enterocytic differentiation, but not on any other cell line isolated from colorectal, breast, and lung cancer. Our data provide evidence that the aberrant functional cell surface expression of an organ-specific chemokine receptor is associated with metastasis to this site. The regulation of receptor function seems to be a critical step in the metastatic process.

Bone marrow contains melanoma-reactive CD8+ effector T cells and, compared with peripheral blood, enriched numbers of melanoma-reactive CD8+ memory T cells.

Circulating melanoma-specific T cells can be frequently detected in patients with melanoma. Effective T-cell immunity and tumor surveillance, however, requires the presence of specific T cells in tissues populated by tumor cells. The bone marrow (BM) is a compartment frequently harboring micrometastatic tumor cells. Here, we compared directly ex vivo in peripheral blood (PB) and BM frequencies and differentiation phenotypes of T cells reactive with the melanoma-associated antigen tyrosinase and with autologous melanoma cells. Using intracellular cytokine and tetramer staining, we detected tyrosinase- and melanoma-reactive CD3+CD8+ T cells in the BM in similar or enhanced frequencies as in PB. Additional characterization of the differentiation subset using CD45RA and CCR7 revealed the presence of specific effector and memory T cells in the BM in all five patients analyzed. Remarkably, the frequency of tyrosinase- and melanoma-specific memory T cells was significantly increased in BM compared with PB. Thus, the BM may be an important compartment for tumor surveillance harboring a tumor-specific memory T-cell pool in addition to effector T cells.