CCR7 in Blood Cancers – Review of Its Pathophysiological Roles and the Potential as a Therapeutic Target

According to the classical paradigm, CCR7 is a homing chemokine receptor that grants normal lymphocytes access to secondary lymphoid tissues such as lymph nodes or spleen. As such, in most lymphoproliferative disorders, CCR7 expression correlates with nodal or spleen involvement. Nonetheless, recent evidence suggests that CCR7 is more than a facilitator of lymphatic spread of tumor cells. Here, we review published data to catalogue CCR7 expression across blood cancers and appraise which classical and novel roles are attributed to this receptor in the pathogenesis of specific hematologic neoplasms. We outline why novel therapeutic strategies targeting CCR7 might provide clinical benefits to patients with CCR7-positive hematopoietic tumors.

Leishmania-Induced Dendritic Cell Migration and Its Potential Contribution to Parasite Dissemination

Leishmania, an intracellular parasite species, causes lesions on the skin and in the mucosa and internal organs. The dissemination of infected host cells containing Leishmania is crucial to parasite survival and the establishment of infection. Migratory phenomena and the mechanisms underlying the dissemination of Leishmania-infected human dendritic cells (hDCs) remain poorly understood. The present study aimed to investigate differences among factors involved in hDC migration by comparing infection with visceral leishmaniasis (VL) induced by Leishmaniainfantum with diverse clinical forms of tegumentary leishmaniasis (TL) induced by Leishmaniabraziliensis or Leishmania amazonensis. Following the infection of hDCs by isolates obtained from patients with different clinical forms of Leishmania, the formation of adhesion complexes, actin polymerization, and CCR7 expression were evaluated. We observed increased hDC migration following infection with isolates of L. infantum (VL), as well as disseminated (DL) and diffuse (DCL) forms of cutaneous leishmaniasis (CL) caused by L. braziliensis and L. amazonensis, respectively. Increased expression of proteins involved in adhesion complex formation and actin polymerization, as well as higher CCR7 expression, were seen in hDCs infected with L. infantum, DL and DCL isolates. Together, our results suggest that hDCs play an important role in the dissemination of Leishmania parasites in the vertebrate host.

A Versatile Toolkit for Semi-Automated Production of Fluorescent Chemokines to Study CCR7 Expression and Functions

Chemokines guide leukocyte migration in different contexts, including homeostasis, immune surveillance and immunity. The chemokines CCL19 and CCL21 control lymphocyte and dendritic cell migration and homing to lymphoid organs. Thereby they orchestrate adaptive immunity in a chemokine receptor CCR7-dependent manner. Likewise, cancer cells that upregulate CCR7 expression are attracted by these chemokines and metastasize to lymphoid organs. In-depth investigation of CCR7 expression and chemokine-mediated signaling is pivotal to understand their role in health and disease. Appropriate fluorescent probes to track these events are increasingly in demand. Here, we present an approach to cost-effectively produce and fluorescently label CCL19 and CCL21 in a semi-automated process. We established a versatile protocol for the production of recombinant chemokines harboring a small C-terminal S6-tag for efficient and site-specific enzymatic labelling with an inorganic fluorescent dye of choice. We demonstrate that the fluorescently labeled chemokines CCL19-S6Dy649P1 and CCL21-S6Dy649P1 retain their full biological function as assessed by their abilities to mobilize intracellular calcium, to recruit β-arrestin to engaged receptors and to attract CCR7-expressing leukocytes. Moreover, we show that CCL19-S6Dy649P1 serves as powerful reagent to monitor CCR7 internalization by time-lapse confocal video microscopy and to stain CCR7-positive primary human and mouse T cell sub-populations.

CONTRIBUTION OF CANCER STEM CELLS TO THE METASTATIC MECHANISM IN POSITIVE LMP I WHO TYPE III NASOPHARYNGEAL CANCER PATIENT BEFORE AND AFTER NEOADJUVANT CHEMOTHERAPY

Introduction Nasopharyngeal cancer is the most common malignant tumour of the head and neck that caused high mortality. Most of patients came for treatment in late stage with enlargement of the neck lymphnode. Cancer stem cells are characteristic of stemness such as self-renewal and survival that caused tumour metastasis and recurrence. CD44, SOX2 and CCR7 are marker for NPC stem cells. Method Nine new patients NPC, WHO type III, positive LMP1 were examined for volume of the neck lymphnode, CD44, SOX2 and CCR7 expression before and after treatment chemotherapy cisplatin based. Staging determined by AJCC/UICC 2010. Result The results of this study showed that all subjects have increased SOX2 and CCR7 expression after treatment with statistically negative correlation. CD44 did not altered before and after treatment and cannot be evaluate. Correlation between alteration of the increase SOX2 and CCR7 expression and reduction of the volume have shown statistically positive correlation. Conclusion Neoadjuvant Chemotherapy Cisplatin based eliminated progenitor cells but did not for cancer stem cells in NPC. This result indicates that NPC with higher cancer stem cells must be more attention forward potential resistance and recurrence of the tumour. Although the have received all Stanford treatment