Cutaneous lymphoma and chemokine

Abstract

The expression pattern of chemokines and chemokine receptors is specific to certain organs and cells. Therefore, chemokines are important to elucidate the mechanism of organ-specific human diseases such as cutaneous lymphoma, characterized by proliferation of clonally expanded lymphocytes in skin without detectable systemic involvement. The most popular type of cutaneous lymphoma is T cell lymphoma, including mycosis fungoides and Sezary syndrome. We have reported that CCL17, CCL27, CCL11, and CCL26 are involved in progression of these diseases. The above chemokines are highly expressed in the lesional skin and serum levels of the chemokines are elevated as the disease progressed. Moreover, CXCL9 and CXCL10 are associated with epidermotropism of tumor cells, CCL21 is important for tumor invasion to lymph nodes, and CXCL12 may explain downregulation of CD26 on the cell surface. CXCL13 expression in lymphoid follicular formation in skin and CCR3 expression on tumor cells in CD30(+) lymphoproliferative disorders are also discussed. Biologics targeting chemokines and their receptors are promising strategies for cutaneous lymphoma. Indeed, humanized anti-CCR4 monoclonal antibody showed potent antitumor activity against CCR4(+) lymphoma cells both in vitro and ex vivo. This antibody may also be useful for allergic diseases such as hay fever. Further study on chemokines and chemokine receptors will be helpful for new classification of cutaneous lymphoma, elucidation of pathogenesis, and development of new therapeutic strategies.