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      OncoTargets and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the pathological basis of cancers, potential targets for therapy and treatment protocols to improve the management of cancer patients. Publishing high-quality, original research on molecular aspects of cancer, including the molecular diagnosis, since 2008. Sign up for email alerts here. 50,877 Monthly downloads/views I 4.345 Impact Factor I 7.0 CiteScore I 0.81 Source Normalized Impact per Paper (SNIP) I 0.811 Scimago Journal & Country Rank (SJR)

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      Treatment with transcatheter arterial chemoembolization induces an increase of the L-selectinlow CXCR3+ CD8+ T cell subset in patients with hepatocellular carcinoma

      OncoTargets and therapy
      Dove Medical Press
      l-selectin, hepatocellular carcinoma, transcatheter arterial chemoembolization, t cells, cxcr3

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          Abstract

          Background The purpose of this study was to investigate the impact of treatment with transcatheter arterial chemoembolization on the expression of chemokine receptors on memory T cells around tumor sites in vivo in patients with hepatocellular carcinoma. Methods Blood samples from the hepatic artery and a peripheral vein were collected from 100 patients with hepatocellular carcinoma before and 4 weeks after treatment with transcatheter arterial chemoembolization. Mononuclear cells were isolated and examined for the expression of L-selectin (CD62L) and CXCR3 (CD183) on CD8+ T cells in patients with hepatocellular carcinoma during transcatheter arterial chemoembolization. Results Both the frequency and number of L-selectinlow CXCR3+ proinflammatory effector T cells in patients with hepatocellular carcinoma increased significantly following treatment versus pretreatment (61.92% ± 8.69% versus 24.45% ± 7.36%, P < 0.05, and 18.98 ± 2.33 e7/L versus 6.10 ± 1.21 e7/L, P < 0.001, respectively). There was no significant difference in its frequency whether in the hepatic artery or peripheral vein. Furthermore, the frequency of CD69+ T cells in patients with hepatocellular carcinoma increased from 2.53% ± 0.51% in the artery and 2.38% ± 0.49% in the vein to 3.80% ± 0.62% and 4.48% ± 0.75%, respectively, after treatment (both P < 0.05). Conclusion Treatment with transcatheter arterial chemoembolization may lead to an increase in L-selectinlow CXCR3+ effector T cells in patients with hepatocellular carcinoma.

          Most cited references27

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          Lineage relationship and protective immunity of memory CD8 T cell subsets.

          Memory CD8 T cells can be divided into two subsets, central (T(CM)) and effector (T(EM)), but their lineage relationships and their ability to persist and confer protective immunity are not well understood. Our results show that T(CM) have a greater capacity than T(EM) to persist in vivo and are more efficient in mediating protective immunity because of their increased proliferative potential. We also demonstrate that, following antigen clearance, T(EM) convert to T(CM) and that the duration of this differentiation is programmed within the first week after immunization. We propose that T(CM) and T(EM) do not necessarily represent distinct subsets, but are part of a continuum in a linear naive --> effector --> T(EM) --> T(CM) differentiation pathway.
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            Chemokines and chemokine receptors: new insights into cancer-related inflammation.

            Chemokines are involved in cellular interactions and tropism in situations frequently associated with inflammation. Recently, the importance of chemokines and chemokine receptors in inflammation associated with carcinogenesis has been highlighted. Increasing evidence suggests that chemokines are produced by tumor cells as well as by cells of the tumor microenvironment including cancer-associated fibroblasts (CAFs), mesenchymal stem cells (MSCs), endothelial cells, tumor-associated macrophages (TAMs) and more recently tumor-associated neutrophils (TANs). In addition to affecting tumor cell proliferation, angiogenesis and metastasis, chemokines also seem to modulate senescence and cell survival. Here, we review recent progress on the roles of chemokines and chemokine receptors in cancer-related inflammation, and discuss the mechanisms underlying chemokine action in cancer that might facilitate the development of novel therapies in the future. Copyright 2010 Elsevier Ltd. All rights reserved.
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              Consequences of Cell Death

              Cell death by necrosis is typically associated with inflammation, in contrast to apoptosis. We have identified additional distinctions between the two types of death that occur at the level of dendritic cells (DCs) and which influence the induction of immunity. DCs must undergo changes termed maturation to act as potent antigen-presenting cells. Here, we investigated whether exposure to apoptotic or necrotic cells affected DC maturation. We found that immature DCs efficiently phagocytose a variety of apoptotic and necrotic tumor cells. However, only exposure to the latter induces maturation. The mature DCs express high levels of the DC-restricted markers CD83 and lysosome-associated membrane glycoprotein (DC-LAMP) and the costimulatory molecules CD40 and CD86. Furthermore, they develop into powerful stimulators of both CD4+ and CD8+ T cells. Cross-presentation of antigens to CD8+ T cells occurs after uptake of apoptotic cells. We demonstrate here that optimal cross-presentation of antigens from tumor cells requires two steps: phagocytosis of apoptotic cells by immature DCs, which provides antigenic peptides for major histocompatibility complex class I and class II presentation, and a maturation signal that is delivered by exposure to necrotic tumor cells, their supernatants, or standard maturation stimuli, e.g., monocyte-conditioned medium. Thus, DCs are able to distinguish two types of tumor cell death, with necrosis providing a control that is critical for the initiation of immunity.
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                Author and article information

                Journal
                22719212
                3377434
                10.2147/OTT.S31816
                https://creativecommons.org/licenses/by-nc/3.0/

                Oncology & Radiotherapy
                l-selectin,hepatocellular carcinoma,transcatheter arterial chemoembolization,t cells,cxcr3

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