Chemokine Receptor Expression in Cutaneous T cell and NK/T-cell Lymphomas: Immunohistochemical Staining and In Vitro Chemotactic Assay

Abstract

Interactions between chemokines and chemokine receptors are involved in migration and invasion of lymphoma cells. We investigated expression profiles of CXCR3 and CCR4 by immunohistochemistry and flow cytometry, and their biologic behaviors by real-time horizontal chemotaxis assay in cutaneous T cell and NK/T-cell lymphomas (TCLs). Tumor cells in mycosis fungoides (MF) constantly expressed CXCR3 at the patch stage, and expressed CCR4 at the tumor stage and in the folliculotropic variant of MF. Neoplastic cells at the plaque stage expressed CXCR3 and/or CCR4. Sezary cells in the dermis and circulation were positive for CCR4. Epidermotropic atypical cells in pagetoid reticulosis expressed CXCR3. CD30 cells exclusively expressed CCR4 in anaplastic large-cell lymphoma, and CXCR3 and/or CCR4 in lymphomatoid papulosis. In CD8TCL and extranodal NK/TCL characterized by extensive epidermotropism, tumor cells were positive for CXCR3. These data demonstrated preferential expression of CXCR3 in epidermotropic tumor cells, and of CCR4 in dermis-based lymphomas. In chemotaxis assays, CCR4 tumor cells in MF and CXCR3 tumor cells in CD8TCL migrated to thymus and activation-regulated chemokine and inducible protein-10, respectively. Therefore, spatial and temporal interactions between chemokine receptors and their ligands seem to dictate recruitment and retention of lymphoma cells in the skin.

Production of Interferon-Inducible Protein-10 and Its Role as an Autocrine Invasion Factor in Nasal Natural Killer/T-Cell Lymphoma Cells

“…On the other hand, it is an accepted fact that nasal NK/T-cell lymphoma cells express CXCR3 on the cell surface. Yagi et al (42) showed CXCR3 expression on the cutaneous NK/T-cell lymphoma cells in all five patients tested with immunohistologic staining. Similarly, Ishida et al (43) showed CXCR3 expression on the nasal NK/T-cell lymphoma cells in 4 (15%) of 27 patients tested with immunohistologic staining.…”

Promiscuous Interaction between Gold-Specific T Cells and APCs in Gold Allergy

“…Briefly, after labeling of target cells with DiOC 18 , effector cells were cocultured with the target cells at an E:T ratio of 10:1 in the absence or presence of gold concentrations ranging from 0.1 to 50 g/ml for 12 h. To enumerate dead target cells, cells stained with propidium iodide were analyzed by FCM. previously described (12). The apparatus consisted of front and back chambers containing cells and a chemoattractant, respectively, which were connected by a microchannel.…”

Cutaneous T-cell Lymphomas

“…What we do know is that the early-stage MF cells show (a) resistance to apoptosis [35] and (b) distinct patterns of chemokine and cytokine receptor expression [10,36]. Progression in MF is associated with shifts in the functional phenotype of the tumor cells reflected in expression of markers such as CD25, CD30, and cytotoxic granule markers [37].…”