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    • Expression of different CD isoforms changes

    2018-10-25

    Expression of different CD45 isoforms changes the recognition of CD45 ligands. For example, the abundance and types of O-glycans on the different CD45 isoforms regulate the cell sensitivity to galectin-1 (Earl et al., 2010). Galectin-1, which is abundantly produced by tumor cells, blocks T cell-mediated cytotoxic responses (Ito et al., 2012) and induces apoptosis of thymocytes and T erk inhibitors (Earl et al., 2010). It is possible that anti-tumor NK cells are selected based on their resistance to galectin-1 or to other ligands through expression of CD45RO. Indeed, as O-glycans bind mainly to CD45 extracellular domain, cells that express short CD45 isoforms, like CD45RO, will have relatively fewer O-glycans and thus will be more resistant to galectin-1. Ex vivo we found very few NK cells that express CD45RO in peripheral blood samples from healthy donors. This is surprising, especially if CD45RO expression identifies memory NK cells, as it has been proposed (Fu et al., 2011). This finding suggests that the amount of memory NK cells might be extremely low in blood or bone marrow samples, or that CD45RO may not be a marker of memory NK cells. Alternatively, CD45RO expression in NK cells could have been specifically lost during ex vivo sample handling. We think that this is unlikely because NK cells express slightly higher levels of total CD45 than other lymphocyte types (data not shown). In fact, we found that CD45RO is mostly associated with effector NK cells; however, differently from what observed in most T cell populations, CD45RA down-regulation is not required for NK cell activation. This suggests that in NK cells the expression of different CD45 isoforms plays a different role than in T cells.
    Financial Support and Acknowledgements All our funders are public or charitable organizations. This work was supported by the program “Chercheur d\'avenir” from the Region Languedoc-Roussillon (09-13195) (MV), a scientific program from the “Communauté de Travail des Pyrénées” (CTPP5/12 to MV), the charities CIEL, L\'Un pour l\'Autre and Ensangble (09/2013) (MV), a grant from FEDER Objectif Competitivite (10-007762) (MV), a grant from the European Community Program SUDOE (CLiNK SOE2/P1/E341 to MV and J-FR), an AOI from the CHU Montpellier (N°221826) (GC and MV) and fellowships from the ARC (DOC20121206007) and La Ligue Contre le Cancer (TDKB13362) (EK) and Ministère de l\'Enseignement Supérieur et de la Recherche (MESR) (DNV). FACs analysis was performed at the platform Montpellier Rio Imaging (MRI).
    Conflicts of Interest
    Introduction Tumors of the lung are one of the highest incidence of cancers and the leading cause of cancer deaths worldwide. According to the 2008 WHO epidemiological statistics, the incidence of lung cancer is more than 130 per 100,000 individuals, which accounts for 13% (1.6 million) of the total cancer cases and 18% (1.4 million) of cancer-related mortality; even worse, the number of new cases is expected to double worldwide in next decades (Jemal et al., 2011). The vast majority (85–90%) of lung cancer cases are non-small-cell lung cancer (NSCLC) (D\'Addario et al., 2010). Early-stage NSCLCs are symptom-free and difficult to detect; therefore, the disease is often diagnosed at a locally advanced or metastatic stage (stage III or stage IV), at which point few clinical treatment options remain. Despite numerous developments relating to NSCLC therapies in recent years, the overall survival rate of NSCLC patients has only improved by approximately 15% over the last few decades (Spiro & Silvestri, 2005; Siegel et al., 2012). In comparison, the five-year survival rate is approximately 33% for cases discovered at early stages (stage I or II) (Little et al., 2005). At present, diagnosis largely relies to a large extent on imaging methods, such as chest X-rays, CT scans, or PET–CT scans, followed by bronchoscopy and biopsy (Oken et al., 2005; International Early Lung Cancer Action Program Investigators et al., 2006). While no blood marker for NSCLC is available at present, some blood-based protein markers such as carcinoembryonic antigen and squamous cell carcinoma antigen have been applied as candidate diagnostic markers for NSCLC in clinics. Unfortunately, the low sensitivity and specificity of these antigens limit the diagnostic accuracy and utility. For these reasons, the development of sensitive and reliable biomarkers remains a major challenge for researchers.