Chemokine receptors are infrequently expressed in malignant and benign mesothelial cells

We studied chemokine receptor expression in malignant mesothelioma (MM), reactive mesothelium (RM), and leukocytes in effusions. The expression of leukocyte markers (CD3, CD4, CD8, CD14, CD16, and CD19) and chemokine receptors (CXCR1, CXCR4, CCR2, CCR5, and CCR7) was studied in 11 MM and 16 RM specimens using flow cytometry. RM specimens showed higher lymphocyte counts (mean rank, 17.6 vs 8.8; P = .004), whereas monocyte numbers were higher in MM (mean rank, 19.5 vs 10.2; P = .002). CXCR1 (P =.006) and CXCR4 (P = .036) expression was higher in MM monocytes. Chemokine receptors were infrequently expressed in MM (0-2/11 effusions per receptor), whereas RM specimens were uniformly negative. Chemokine receptors are widely expressed on leukocytes in MM and RM effusions but are infrequently found on cells of mesothelial origin. This finding suggests a major role for an autocrine chemokine pathway in leukocytes but not in MM cells. The increased monocyte infiltration and their higher chemokine receptor expression in MM effusions may have a tumor-promoting rather than tumor-inhibiting effect.     

Chemokine receptors that mediate B cell homing to secondary lymphoid tissues are highly expressed in B cell chronic lymphocytic leukemia and non-Hodgkin lymphomas with widespread nodular dissemination

B cell neoplasms present heterogeneous patterns of lymphoid organ involvement, which may be a result of the differential expression of chemokine receptors. We found that chemokine receptor (CCR)7, CXC chemokine receptor (CXCR)4, or CXCR5, the main chemokine receptors that mediate B cell entry into secondary lymphoid tissues and their homing to T cell and B cell zones therein, were highly expressed in B malignancies with widespread involvement of lymph nodes. Conversely, those pathologies with little or no nodular dissemination showed no expression to very low levels of CCR7 and CXCR5 and low to moderate levels of CXCR4. These findings provide evidence for the role of CCR7, CXCR4, and CXCR5 in determining the pattern of lymphoid organ involvement of B tumors. Functional studies were performed on B malignancies expressing different levels of CCR7, CXCR5, and CXCR4. Multiple myeloma (MM) cells did not express CCR7 nor CXCR5 and did not migrate in response to their ligands; a moderate expression of CXCR4 on MM cells was accompanied by a migratory response to its ligand, CXCL12. By contrast, cells from B cell chronic lymphocytic leukemia (B-CLL) expressed the highest levels of these chemokine receptors and efficiently migrated in response to all ligands of CCR7, CXCR4, and CXCR5. In addition, the migration index of B-CLL cells in response to both of the CCR7 ligands correlated with the presence of clinical lymphadenopathy, thus indicating that the high expression of functional chemokine receptors justifies the widespread character of B-CLL, representing a clinical target for the control of tumor cell dissemination.     

Expression and functional activity of chemokine receptors in glatiramer acetate-specific T cells isolated from multiple sclerosis patient receiving the drug glatiramer acetate

The purpose of the current study is to examine the surface expression of chemokine receptors and the chemotaxis toward the respective chemokines of glatiramer acetate (GA)-specific CD4(+) T cells isolated from the blood and the cerebrospinal fluid (CSF) of a multiple sclerosis (MS) patient. Four clones were selected, two isolated from the peripheral blood and two from the CSF. CCR4 and CXCR3 were expressed on all four clones. Both blood-derived clones also expressed CCR5 and, to a lesser extent, CCR6. Similarly, one CSF clone expressed CCR5 and CCR6. In contrast, CCR1, CCR2, CCR3, CCR7, CCR9, CCR10, CXCR1, CXCR4, CXCR5, CXCR6, and CCR6 were either expressed on few cells or were not expressed at all on all four clones examined. The expression of chemokine receptors was corroborated with the ability of the cells to respond chemotactically to the corresponding chemokines, CCL5/RANTES, CCL20/MIP-3α, CCL22/MDC and CXCL10/IP-10. Both the receptor expression and chemotaxis were reduced upon activation with PMA and ionomycin. The shared expression of chemokine receptors and the migration patterns suggest that GA-reactive cells have migrated from the blood into the CSF, and that local reactivation within the inflamed CSF may downregulate the expression of chemokine receptors and hence impede their migration intrathecally. The results may also explain the beneficial synergistic effects of combining immunosuppressive drugs with GA in MS patients.     

Chemokine receptor expression on human eosinophils from peripheral blood and bronchoalveolar lavage fluid after segmental antigen challenge

BACKGROUND: The recruitment of circulating eosinophils to the lung is a characteristic feature of allergic airway inflammation. Chemokine receptors likely play a role in this complex process. However, reports of chemokine receptor expression on human eosinophils are conflicting. OBJECTIVE: The aim of this study was to determine whether the chemokine receptor profile of human eosinophils change when these cells are recruited to the airway after an antigen challenge and development of an allergic inflammatory response. METHODS: Blood and bronchoalveolar lavage (BAL) cells were obtained from 13 allergic subjects 48 hours after segmental bronchoprovocation with antigen. The CC chemokine receptor (CCR) 1 to 7, 9, and CXC chemokine receptor (CXCR) 1 to 4 were determined by flow cytometric analysis of whole blood and unseparated BAL cells. RESULTS: Compared with their circulating counterparts, airway eosinophils had decreased CCR3 and increased CCR4, CCR9, and CXCR3 expression on their cell surface. Furthermore, expression of CCR3, CCR4, and CXCR3 was significantly correlated with the percentage of eosinophils in BAL fluid at 48 hours. Eosinophils also expressed CXCR4, but this receptor did not change after antigen-induced recruitment to the airway. In contrast, the expression of CCR1, CCR2, CCR5, CCR6, CCR7, CXCR1, and CXCR2 remained undetectable on either blood or BAL eosinophils. CONCLUSIONS: Our data suggest that recruitment of eosinophils to the airway is associated with a modulation of their chemokine receptor profiles. These changes in chemokine receptors could be involved in determining eosinophil function and antigen-induced airway inflammation.     

The Differential Expression and Function of the Inflammatory Chemokine Receptor CXCR5 in Benign Prostatic Hyperplasia and Prostate Cancer

Background: Chemokine and chemokine receptors could have played an important role in tumor angiogenesis and distant metastasis. The mechanism of inflammation, expression and function of chemokines and chemokine receptors in benign prostatic hyperplasia (BPH) and prostate cancer (PCa) remain unclear. The purpose of present study is to detect differential expression and function of chemokines and chemokine receptors (CCRs) in BPH and PCa.Methods: BPH-1 and peripheral blood mononuclear cells (PBMCs) were co-cultured in Transwell chambers, and human normal prostate (NP) tissues, BPH tissues and PCa tissues were collected. CCR gene-chips were used to analyze and compare the differential expression of CCRs in BPH-1 cells, BPH-1 cells co-cultured with PBMCs, and LNCaP cells. The differential expression of CCRs was detected and validated using real-time PCR, western blotting and immunofluorescence (IF). The proliferation of LNCaP cells was also investigated after the knockdown CXCR5.Results: Results of gene-chips indicated that there was low or no expression of CCR10, CXCR1, CXCR3 and CXCR5 in BPH-1 cells, whereas the expression of these receptors in BPH-1 cells was increased by PBMCs, and the expression was high in LNCaP cells. Furthermore, real-time PCR and western blotting confirmed the above mentioned results. IF verified no or low expression of CXCR1, CXCR3 and CXCR5 in NP tissues, low or moderate expression in BPH and high expression in PCa. However, CCR10 was not expressed at detectable levels in the three groups. The growth and proliferation of LNCaP cells was markedly inhibited after down-regulation of CXCR5.Conclusions: PCa cells expressed high levels of CCR10, CXCR1, CXCR3 and CXCR5. Although BPH cells did not express these factors, their expression was up-regulated when BPH-1 cells were incubated with inflammatory cells. Finally, down-regulation of CXCR5 inhibited the growth and proliferation of LNCaP cells.     

Chemokine receptor expression profile of eosinophils at inflamed tissue sites: Decreased CCR3 and increased CXCR4 expression by lung eosinophils

BACKGROUND: To date, most studies dealing with eosinophil chemokine receptors have used eosinophils isolated from peripheral blood. During the movement of eosinophils from the peripheral blood to inflamed tissue sites, microenvironmental signals might alter their expression of chemokine receptors. However, little is known about the profile of expression of chemokine receptors by eosinophils at inflamed tissue sites in human beings. OBJECTIVE: The purpose of this study was to determine whether eosinophils that have migrated into inflamed tissues exhibit a profile of chemokine receptor expression that is qualitatively and/or quantitatively different from that of eosinophils in peripheral locations. METHODS: We studied simultaneously the expression and function of chemokine receptors in eosinophils in both bronchoalveolar lavage fluid (BALF) and peripheral blood specimens of 7 patients with eosinophilic lung diseases. RESULTS: De novo expression of CCR2, CCR4, and CCR5 was not detected at either the protein or the mRNA level. However, surface expression of CCR3 was decreased and CXCR4 was conversely increased with statistical significance in BALF eosinophils. Moreover, the changes in CCR3 and CXCR4 expression were reflected in the altered migratory response to their ligands. On the other hand, the levels of CXCR1, CXCR2, CXCR3, and CCR1 were virtually unchanged in BALF eosinophils, and these receptors did not have functional significance. CONCLUSION: Eosinophils at inflamed tissue sites exhibited an expression profile qualitatively similar to that in peripheral locations, except for decreased CCR3 and increased CXCR4 expression. Our results suggest that CCR3 is primarily and CXCR4 is cooperatively involved in eosinophil accumulation at inflamed tissue sites.     

Airway smooth muscle chemokine receptor expression and function in asthma

Background Chemokine receptors play an important role in cell migration and wound repair. In asthma, CCR3 and 7 are expressed by airway smooth muscle (ASM) and CCR7 has been implicated in the development of ASM hyperplasia. The expression profile of other chemokine receptors by ASM and their function needs to be further explored.
Objective We sought to investigate ASM chemokine receptor expression and function in asthma.
Methods ASM cells were derived from 17 subjects with asthma and 36 non-asthmatic controls. ASM chemokine receptor expression was assessed by flow cytometry and immunofluorescence. The function of chemokine receptors expressed by more than 10% of ASM cells was investigated by intracellular calcium measurements, chemotaxis, wound healing, proliferation and survival assays.
Results In addition to CCR3 and 7, CXCR1, 3 and 4 were highly expressed by ASM. These CXC chemokine receptors were functional with an increase in intracellular calcium following ligand activation and promotion of wound healing [CXCL10 (100 ng/mL) 34 ± 2 cells/high-powered field (hpf) vs. control 29 ± 1; P =0.03; n =8]. Spontaneous wound healing was inhibited by CXCR3 neutralizing antibody (mean difference 7 ± 3 cells/hpf; P =0.03; n =3). CXC chemokine receptor activation did not modulate ASM chemotaxis, proliferation or survival. No differences in chemokine receptor expression or function were observed between ASM cells derived from asthmatic or non-asthmatic donors.
Conclusions Our findings suggest that the chemokine receptors CXCR1, 3 and 4 modulate some aspects of ASM function but their importance in asthma is uncertain.     

Immunohistochemical Analysis of CXCR4 Expression in Fibrohistiocytic Tumors

Functional chemokine receptors are expressed in many malignant tumors. These receptors promote tumor growth and metastasis in response to endogenous chemokines. We analyzed the expression of CXCR4, CCR6 and CCR7 in fibrohistiocytic tumors, including dermatofibrosarcoma protuberance (DFSP), malignant fibrous histiocytoma (MFH), dermatofibroma (DF) using immunohistochemistry. We also investigated the relationship between CXCR4 and CD34, the latter of which is an immunohistochemical marker for DFSP. We observed a higher expression of CXCR4 in DFSP and MFH as compared with DF. Interestingly, a significantly higher expression of CXCR4 was detected in relapsed DFSP than in non-relapsed DFSP, but no significant differences were detected between non-relapsed DFSP and DFSP with CD34 immunostaining. Moreover, MFH had strong immunoreactivity for CXCR4, CCR6 and CCR7. These findings suggest that the assessment of CXCR4 immunoreactivity in fibrohistiocytic tumors is a useful tool for predicting tumor aggressiveness.     

CCR4 memory CD4+ T lymphocytes are increased in peripheral blood and lesional skin from patients with atopic dermatitis

BACKGROUND: Recent studies have reported that TH1 and TH2 cells express CXCR3 and CCR4, respectively. OBJECTIVE: Our goal was to assess the association of CCR4 and CXCR3 expression with TH2 and TH1 cells and association of CCR4 and CXCR3 expression with inflammation in patients with atopic dermatitis (AD). METHODS: Intracellular cytokine production and chemokine receptor expression in blood T cells were examined by flow cytometry. Immunohistochemical expression of chemokine receptors was also investigated in chronically lesional skin. RESULTS: CCR4+ and CXCR3+ CD4+ T cells predominantly produced IL-4 and IFN-gamma, respectively. Although the frequency of CXCR3+ cells among CD4+ CD45RO+ T cells was similar for patients with AD (n = 29) and healthy control subjects (n = 19), patients with severe AD (n = 14) had a reduced frequency of CXCR3+ cells. In contrast, the frequency of CCR4+ cells and the CCR4/CXCR3 ratio were higher in patients with AD (n = 22) than healthy control subjects (n = 16) and correlated with disease severity of AD. The frequency of CCR4+ cells correlated positively with eosinophil numbers and serum IgE levels, whereas the frequency of CXCR3+ cells correlated inversely with eosinophil numbers. The frequency of CCR4+ or CXCR3+ cells was similar in patients with psoriasis (n = 6) and healthy control subjects. Immunohistochemical analysis showed that the frequency of CCR4+ cells among CD4+ T cells in chronically lesional skin of patients with AD (n = 9) was higher than that of patients with psoriasis (n = 4). CONCLUSION: Our data suggest the association of CCR4 expression with TH2 cells, the predominance of CCR4+ cells in blood from patients with AD, and an important role of CCR4 in the migration of TH2 cells from blood into AD lesional skin.     

Molecular trafficking mechanisms of multipotent mesenchymal stem cells derived from human bone marrow and placenta

We compared potential trafficking mechanisms used by human (h) multipotent mesenchymal stem cells (MSC) derived from bone marrow (bm) or placenta (p). Both hbmMSC and hpMSC expressed a broad range of cell surface adhesion molecules including beta1-integrins (CD29) and CD44. Array data showed that both hbmMSC and hpMSC expressed mRNA for the cell adhesion molecules CD54 (ICAM-1), E-cadherin, CD166 (ALCAM), CD56 (NCAM), CD106 (VCAM-1), CD49a, b, c, e and f (integrins alpha1, 2, 3, 4 and 6), integrin alpha11, CD51 (integrin alphaV), and CD29 (integrins beta1). Functional binding of hpMSC, but not hbmMSC to VCAM-1 was demonstrated using recombinant chimeric constructs. Neither bone marrow nor placental MSC expressed ligands to endothelial selectins such as PSGL-1 or sialyl Lewis X (sLe(x)) carbohydrates and neither were able to bind functionally to chimeric constructs of the endothelial selectins CD62E (E-selectin) and CD62P (P-selectin). Furthermore, MSC expressed a restricted range of transferases necessary for expression of sLe(x), with no detectable expression of fucosyl transferases IV or VII. Placental MSC, but not hbmMSC, expressed mRNA for the chemokine receptors CCR1 and CCR3, and both hbmMSC and hpMSC expressed mRNA for CCR7, CCR8, CCR10, CCR11, CXCR4 and CXCR6. Intracellular chemokine receptor protein expression of CCR1, CCR3, CXCR3, CXCR4 and CXCR6 was detected in both hbmMSC and hpMSC. Cell surface expression of chemokine receptors was much more restricted with only CXCR6 displaying a strong signal on hbmMSC and hpMSC. Although cell surface expression of CXCR4 was not detected, MSC migrated in response to its ligand, CXCL12 (SDF-1). Thus, hbmMSC and hpMSC have an almost identical profile for cell surface adhesion and chemokine receptor molecules at the mRNA and protein levels. However, at the functional level, hpMSC likely utilise VLA-4-mediated binding in a superior manner to hbmMSC and thus may have superior engraftment properties to hbmMSC in vivo.     

趋化因子受体CCR5、CCR7、CXCR3和CXCR6在丙肝患者肝内及外周血CD4+ T淋巴细胞上的表达及其意义

目的比较趋化因子受体CCR5、CCR7、CXCR3和CXCR6在丙肝患者肝内和外周血CD4^＋T淋巴细胞表面表达水平及其意义,同时进一步了解其与肝脏组织学炎症反应的关系.方法采用荧光标记抗趋化因子受体的单克隆抗体对肝内及外周血中CD4^＋T淋巴细胞表面的趋化因子受体进行染色后,采用9色11参数流式细胞仪LSRⅡ进行检测分析.结果（1）肝内CCR5^＋、CXCR3^＋或/和CXCR6^＋的CD4^＋T淋巴细胞频数高于外周血（P＜0.001）,而CCR7^＋CD4^＋T淋巴细胞频数低于外周血（P＜0.001）;（2）肝内CCR5^＋或CXCR6^＋的活性（CD38^＋）CD4^＋T淋巴细胞频数高于外周血（P＜0.05）;（3）肝内表达2种或2种以上趋化因子受体CCR5、CXCR3和CXCR6的CD4^＋T淋巴细胞频数明显高于外周血（P＜0.001）,而不表达或仅表达一种上述趋化因子受体CD4^＋T淋巴细胞频数明显低于外周血（P＜0.001）;（3）CCR5和CXCR6在肝内CD4^＋T淋巴细胞表面的表达有中等度相关;（4）肝内组织学炎症明显组表达趋化因子受体CCR5、CXCR3或CXCR6的CD4^＋T淋巴细胞频数高于炎症轻微组.结论趋化因子受体CCR5、CXCR3和CXCR6可能介导CD4^＋T淋巴细胞向肝内迁徙定植,并参与肝脏炎症的病理免疫学反应过程.     

CXCR6 and CCR5 localize T lymphocyte subsets in nasopharyngeal carcinoma

The substantial T lymphocyte infiltrate found in cases of nasopharyngeal carcinoma (NPC) has been implicated in the promotion of both tumor growth and immune escape. Conversely, because malignant NPC cells harbor the Epstein-Barr virus, this tumor is a candidate for virus-specific T cell-based therapies. Preventing the accumulation of tumor-promoting T cells or enhancing the recruitment of tumor-specific cytotoxic T cells offers therapeutic potential. However, the mechanisms involved in T cell recruitment to this tumor are poorly understood. Comparing memory T cell subsets that have naturally infiltrated NPC tissue with their counterparts from matched blood revealed enrichment of CD8(+), CD4(+), and regulatory T cells expressing the chemokine receptor CXCR6 in tumor tissue. CD8(+) and (nonregulatory) CD4(+) T cells also were more frequently CCR5(+) in tumor than in blood. Ex vivo studies demonstrated that both receptors were functional. CXCL16 and CCL4, unique chemokine ligands for CXCR6 and CCR5, respectively, were expressed by the malignant cells in tumor tissue from the majority of NPC cases, as was another CCR5 ligand, CCL5. The strongest expression of CXCL16 was found on tumor-infiltrating cells. CCL4 was detected on the tumor vasculature in a majority of cases. These findings suggest that CXCR6 and CCR5 play important roles in T cell recruitment and/or retention in NPC and have implications for the pathogenesis and treatment of this tumor.     

人早孕期绒毛组织和滋养细胞趋化因子受体转录水平

目的：研究早孕期绒毛组织及滋养细胞18种趋化因子受体的转录水平，以揭示趋化因子受体在母一胎界面生理性调节作用。方法：提取人早孕期绒毛组织及滋养细胞总RNA，半定量RT-PCR检测绒毛组织和滋养细胞18种趋化因子受体mRNA的表达水平。结果：CXCR4及CXCR6在绒毛组织中普遍高表达；CCR6、CCR7、XCR1及CX3CR1呈普遍中等表达；CCR1～CCR5、CCR8～CCR10、CXCR1～CXCR3在部分绒毛组织中表达，部分绒毛组织不表达或表达量很低；早孕人绒毛组织不表达CXCR5。早孕期滋养细胞表达CCR1、CCR3～CCR5、CCR8～CCR9、CXCR1～CXCR4、CXCR6、XCR1、CX3CR1；不表达CCR2、CCR6、CCR7、CCR10及CXCR5。结论：早孕期绒毛组织及滋养细胞表达多种趋化因子受体，它们在正常妊娠中具有重要的生理学意义。     

NK- and B-cell infiltration correlates with worse outcome in metastatic ovarian carcinoma

We studied the clinical role of leukocyte infiltration and chemokine receptor expression in ovarian carcinoma effusions. Expression of leukocyte markers (CD3, CD4, CD8, CD4/CD8 ratio, CD16, CD19, and CD14) and chemokine receptors (CXCR1, CXCR4, CCR2, CCR5, and CCR7) was studied in 73 effusions by using flow cytometry. CXCR4, CCR5, and CCR7 were expressed abundantly on leukocytes, but all receptors were expressed rarely on cancer cells. The presence of natural killer cells (P = .042) and International Federation of Gynecology and Obstetrics (FIGO) stage IV disease (P = .024) predicted worse overall survival (OS). A higher percentage of CD19+ cells (P = .015) and stage IV disease (P = .008) predicted poor survival for patients with postchemotherapy effusions. Only FIGO stage retained significance as a predictor of OS (P = .035) in multivariate analysis. Chemokine receptors are expressed widely on leukocytes but rarely on carcinoma cells in ovarian carcinoma effusions, arguing against an autocrine chemokine pathway in this malignancy. Immune response parameters in ovarian cancer effusions are weak predictors of outcome.     

Distinct signatures of B-cell homeostatic and activation-dependent chemokine receptors in the development and progression of extragastric MALT lymphomas

Chemokine receptors mediate migration and activation of lymphocytes through binding of their ligands. Recent studies have revealed important contributions of chemokine receptors to the development, progression, and dissemination of haematopoietic neoplasms. Because the chemokine receptor expression profile in extragastric MALT lymphoma is unknown, we performed a comprehensive study on tissue samples of parotid glands, parotid glands affected by Sjögren syndrome, extragastric MALT lymphoma, and extranodal diffuse large B‐cell lymphoma (eDLBCL) originating from MALT lymphoma (transformed MALT lymphoma). By investigating the expression of 19 chemokine receptors by real‐time PCR using a semi‐quantitative approach and of four chemokine receptors (CCR1, CCR5, CXCR6, and XCR1) by immunohistochemistry, we show that the chemokine receptor expression profiles of extragastric MALT lymphomas differ substantially from those of extranodal DBLCL, with lower expression of CCR1, CCR8, and CXCR3, and the absence of expression of CX3CR1 and XCR1 in eDLBCL. Expression of CCR6, CCR7, CXCR3, CXCR4, and CXCR5, responsible for B‐cell homing to secondary lymphoid tissue, was detected in both B‐cell malignancies. Expression of CCR4 was just detected in trisomy 3‐positive MALT lymphoma cases. Comparing gastric with extragastric MALT lymphomas, up‐regulation of CXCR1 and CXCR2 accompanied by down‐regulation of CCR8 and CX3CR1 and loss of XCR1 expression in extragastric MALT lymphomas appear to be key determinants for the site of origin of MALT lymphomagenesis. Our results support a model of stepwise progression of extragastric MALT lymphoma from a non‐neoplastic event to Sjögren syndrome, to MALT lymphoma, and finally to overt eDLBCL, guided by differentially expressed B‐cell homeostatic and activation‐dependent chemokine receptors and their ligands. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Kinetics and expression patterns of chemokine receptors in human CD4+ T lymphocytes primed by myeloid or plasmacytoid dendritic cells

We investigated the kinetics of expression of 12 chemoattractant receptors as a function of cell division following priming of human naive CD4+ T cells by different populations of dendritic cells (DC) and under conditions favoring Th1 or Th2 differentiation. Two chemokine receptors, CXCR3 and CXCR5, were rapidly up-regulated following T cell activation by either monocyte-derived DC, myeloid DC (mDC) or plasmacytoid DC (pDC). While CXCR5 expression was transient, expression of CXCR3 at advanced cell divisions was dependent on differentiation, being expressed at high levels on Th1 cells. Several other receptors (CCR2, CCR3, CCR4, CCR5, CXCR6 and CRTh2) were acquired progressively as a function of cell division and in a fashion that was influenced by polarizing cytokines. The Th2-associated chemoattractant receptors CRTh2 and CCR3 were up-regulated with slower kinetics compared to the Th1-associated receptors CXCR3 and CXCR6, consistent with a different kinetics and efficiency of polarization. Moreover, CCR4 and CXCR6 were preferentially induced in T cells activated by mDC and pDC, respectively. Finally, CXCR5 and CCR7 were also rapidly and transiently up-regulated in memory T cells following TCR stimulation. These results indicate a complex chemokine receptor regulation dependent on both T cell activation and differentiation state. In addition, they reveal the existence of DC-specific cues for the regulation of T cell migratory capacity.     

Chemokine Receptor CXCR4 Is a Novel Marker for the Progression of Cutaneous Malignant Melanomas

The CXCR4/CXCL12 pathway has recently been reported to be involved in stimulating the metastasis of many different neoplasms, in which CXCR4 activates various phenomena such as chemotaxis, invasion, angiogenesis and proliferation. The purpose of this study was to analyze a possible association between the expression of chemokine receptors CXCR4, CCR6 and CCR7 with the clinicopathological features of cutaneous malignant melanoma, and to assess the usefulness of these chemokine receptors for diagnosis and prognosis. In our study, a percentage of immunoexpression of both CXCR4 and its ligands CXCL12 was associated with high clinical risk. In contrast, the patients with a low immunoexpression of CXCR4 and CXCL12 had low clinical risk. CCR6 and CCR7 immunoexpressions were also correlated with some clinical parameters, but seemed no more useful than CXCR4. These data suggest that the assessment of CXCR4 immunoexpression is a novel tool for predicting tumor aggressiveness in malignant melanomas, and in particular, a high immunoexpression percentage of CXCR4 and CXCL12 might be a sign of a poor prognosis.