CD1d expression as a prognostic marker for chronic lymphocytic leukemia

Anastasiadis, Athanasios; Kotsianidis, Ιoannis; Papadopoulos, Vassilios; Spanoudakis, Emmanouil; Margaritis, Dimitrios; Christoforidou, Anna; Gouliamtzi, Stamatoula; Tsatalas, Costas

doi:10.3109/10428194.2013.803222

Cited by 17 publications

(11 citation statements)

References 15 publications

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“…Another means by which tumor cells escape NKT cell-mediated antitumor response was shown in a mouse model of lymphoma, where shedding of tumor-associated glycolipids was shown to inhibit CD1-mediated presentation to NKT cells ( 101 ). Interestingly, in chronic lymphocytic leukemia (CLL), CD1d expression was found to increase during disease progression, counteracting the suggested role of CD1d as an anti-survival factor in cancer ( 102 , 103 ). However, a recent study has shown that higher CD1d expression on CLL cells associated with disease progression actually led to impairment in both function and numbers of type I NKT cells ( 104 ).…”

Section: Direct Cytotoxicity Against Tumor Cellsmentioning

confidence: 99%

Natural Killer T Cells in Cancer Immunotherapy

2017

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Natural killer T (NKT) cells are specialized CD1d-restricted T cells that recognize lipid antigens. Following stimulation, NKT cells lead to downstream activation of both innate and adaptive immune cells in the tumor microenvironment. This has impelled the development of NKT cell-targeted immunotherapies for treating cancer. In this review, we provide a brief overview of the stimulatory and regulatory functions of NKT cells in tumor immunity as well as highlight preclinical and clinical studies based on NKT cells. Finally, we discuss future perspectives to better harness the potential of NKT cells for cancer therapy.

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Section: Direct Cytotoxicity Against Tumor Cellsmentioning

confidence: 99%

Natural Killer T Cells in Cancer Immunotherapy

2017

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“…While type I NKT cells harbor a conserved invariant TCR (thus giving rise to the term invariant or iNKT), preferably consisting of TCR-Vβ11 in combination with an invariant Vα24 in humans and TCR-Vβ2, TCR-Vβ7, TCR-Vβ8.2 in mice, type II NKT cells express a more diverse TCR repertoire [12]. In CLL, CD1d has recently been shown to be aberrantly expressed and its expression level was predictive for a poor clinical outcome [13–14]. Concomitantly, CD56 + T cells, which are an NKT-like population, were shown to be decreased in progressive CLL patients [15].…”

Section: Introductionmentioning

confidence: 99%

CD1d expression on chronic lymphocytic leukemia B cells affects disease progression and induces T cell skewing in CD8 positive and CD4CD8 double negative T cells

et al. 2016

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Chronic lymphocytic leukemia develops within a complex network driven by genetic mutations and microenvironmental interactions. Among the latter a complex interplay with the immune system is established by the clone. Next to a proposed recruitment of support from T and myeloid cells, potential anti-CLL immune reactions need to be subverted.By using TCL1 mice as a CLL model, we show that TCR-Vβ7+ NK1.1+ T cells are overrepresented in this disease model and constitute a main subset of peripheral CD3+ cells with biased TCR usage, showing that these cells account for a major part for T cell skewing in TCL1 mice. Moreover, we show that overrepresentation is dependent on CD1d expression in TCL1 mice, implicating that these cells belong to a NKT-like cell fraction which are restricted to antigen presented by the MHC-like surface marker CD1d. Accordingly, we observed a high fraction of CD161+ cells within overrepresented T cells in CLL patients and we found downregulation of CD1d on the surface of CLL cells, both in TCL1 mice and patients. Finally, we show that in TCL1 mice, CD1d deficiency resulted in shortened overall survival. Our results point to an interaction between CLL and CD161+ T cells that may represent a novel therapeutic target for immune modulation.

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“…Previous few studies demonstrated an association between CD1d expression and the adverse immunophenotypic feature, namely CD38 expression in CLL patients [13,24] . By contrast, another research group detected no significant differences between Zap-70 positive and negative, CD38 positive and negative CLL sub groups [25] .…”

Section: Discussionmentioning

confidence: 99%