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[Cancer Research 66, 5716-5722, June 1, 2006]
© 2006 American Association for Cancer Research

Cell, Tumor, and Stem Cell Biology

Specific Recruitment of CC Chemokine Receptor 4–Positive Regulatory T Cells in Hodgkin Lymphoma Fosters Immune Privilege

Takashi Ishida1, Toshihiko Ishii1, Atsushi Inagaki1, Hiroki Yano1, Hirokazu Komatsu1, Shinsuke Iida1, Hiroshi Inagaki2 and Ryuzo Ueda1

Departments of 1 Internal Medicine and Molecular Science and 2 Clinical Pathology, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho-chou, Mizuho-ku, Nagoya-shi, Aichi, Japan

Requests for reprints: Takashi Ishida, Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-chou, Mizuho-ku, Nagoya, Aichi 467-8601, Japan. Phone: 81-52-853-8216; Fax: 81-52-852-0849; E-mail: itakashi{at}med.nagoya-cu.ac.jp.

Hodgkin lymphoma (HL) is characterized by the presence of a small number of tumor cells in a rich background of inflammatory cells, but the contribution of the abundant nontumor cells to HL pathogenesis is poorly understood. We showed that migratory CD4+ cells induced by HL cells were hyporesponsive to T-cell receptor stimulation and suppressed the activation/proliferation of the effector CD4+ T cells in an autologous setting. We further showed that HL cells in the affected lymph nodes were surrounded by a large number of lymphocytes expressing both CC chemokine receptor 4 (CCR4) and FOXP3. These findings indicate that the migratory cells induced by HL cells function as regulatory T (Treg) cells so that these cells create a favorable environment for the tumor cells to escape from host immune system. In addition, we showed that a chimeric anti-CCR4 monoclonal antibody (mAb) could deplete CCR4+ T cells and inhibit the migration of CD4+CD25+ T cells in vitro. Recognition of the importance of CCR4+ Treg cells in the pathogenesis of HL will allow rational design of more effective treatments, such as use of an anti-CCR4 mAb, to overcome the suppressive effect of CCR4+ Treg cells on the host immune response to tumor cells. (Cancer Res 2006; 66(11): 5716-22)




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