Summary• Plant invasion potentially alters ecosystem carbon (C) and nitrogen (N) cycles. However, the overall direction and magnitude of such alterations are poorly quantified.• Here, 94 experimental studies were synthesized, using a meta-analysis approach, to quantify the changes of 20 variables associated with C and N cycles, including their pools, fluxes, and other related parameters in response to plant invasion.• Pool variables showed significant changes in invaded ecosystems relative to native ecosystems, ranging from a 5% increase in root carbon stock to a 133% increase in shoot C stock. Flux variables, such as above-ground net primary production and litter decomposition, increased by 50-120% in invaded ecosystems, compared with native ones. Plant N concentration, soil and concentrations were 40, 30 and 17% higher in invaded than in native ecosystems, respectively. Increases in plant production and soil N availability indicate that there was positive feedback between plant invasion and C and N cycles in invaded ecosystems.• Invasions by woody and N-fixing plants tended to have greater impacts on C and N cycles than those by herbaceous and nonN-fixing plants, respectively. The responses to plant invasion are not different among forests, grasslands, and wetlands. All of these changes suggest that plant invasion profoundly influences ecosystem processes.Key words: carbon and nitrogen pools and fluxes, litter quality, meta-analysis, plant invasion, soil nitrogen availability.New Phytologist (2008) 177: 706-714

BackgroundChimeric antigen receptor (CAR)-engineered T cells have demonstrated promising clinical efficacy in patients with B cell lymphoma. However, the application of CAR-T cell therapy in the treatment of other solid tumors has been limited. We incorporated 4-1BB into the anti-GD2 CAR-T cells to test their cytotoxicity in melanoma in vitro and in vivo. Moreover, we reported the expression of ganglioside GD2 in non-Caucasian melanoma populations for the first time, thus providing a basis for future clinical research.MethodsThis study included tumor samples from 288 melanoma patients at the Peking University Cancer Hospital & Institute. Clinical data were collected. Immunohistochemical assays using antibodies against ganglioside GD2 were performed on formalin-fixed, paraffin-embedded specimens. The ability of ganglioside GD2 CAR-T cells to kill ganglioside GD2+ melanoma cells was evaluated in vitro and in a patient-derived xenograft (PDX) model.ResultsAmong the 288 samples, 49.3% of cases (142/288) demonstrated positive staining with ganglioside GD2. The median survival time in patients exhibiting ganglioside GD2 expression was significantly shorter than that in patients without ganglioside GD2 expression (31 vs. 47.1 months, P < 0.001). In the present study, CAR was constructed using a GD2-specific scFv (14.G2a), T cell receptor CD3ζ chain, and the CD137 (4-1BB) costimulatory motif. In addition, the GD2.BBζ CAR-T cells demonstrated specific lysis of ganglioside GD2-expressing melanoma cells in vitro. In two PDX models, mice that received intravenous or local intratumor injections of GD2.BBζ CAR-T cells experienced rapid tumor regression.ConclusionsThese data demonstrate that the rate of GD2 expression in Chinese patients is 49.3%. GD2.BBζ CAR-T cells can both efficiently lyse melanoma in a GD2-specific manner and release Th1 cytokines in an antigen-dependent manner in vitro and in vivo. Anti-GD2/4-1BB CAR-T cells represent a clinically appealing treatment strategy for Chinese melanoma patients exhibiting GD2 expression and provide a basis for future studies of the clinical application of immunotherapy for melanoma.Electronic supplementary materialThe online version of this article (10.1186/s13045-017-0548-2) contains supplementary material, which is available to authorized users.

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Purpose: Effective therapies for the majority of metastatic acral melanoma patients have not been established. Thus, we investigated genetic aberrations of CDK4 pathway in acral melanoma and evaluated the efficacy of CDK4/6 inhibitors in targeted therapy of acral melanoma.Experimental Design: A total of 514 primary acral melanoma samples were examined for the copy number variations (CNV) of CDK4 pathway-related genes, including Cdk4, Ccnd1, and P16 INK4a , by QuantiGenePlex DNA Assay. The sensitivity of established acral melanoma cell lines and patient-derived xenograft (PDX) containing typical CDK4 aberrations to CDK4/6 inhibitors was evaluated.Results: Among the 514 samples, 203 cases, 137 cases, and 310 cases, respectively, showed Cdk4 gain (39.5%), Ccnd1 gain (26.7%), and P16INK4a loss (60.3%). The overall frequency of acral melanomas that contain at least one aberration in Cdk4, Ccnd1, and P16 INK4a was 82.7%. The median overall survival time for acral melanoma patients with concurrent Cdk4 gain with P16INK4a loss was significantly shorter than that for patients without such aberrations (P ¼ 0.005). The pan-CDK inhibitor AT7519 and selective CDK4/6 inhibitor PD0332991 could inhibit the cell viability of acral melanoma cells and the tumor growth of PDX with Cdk4 gain plus Ccnd1 gain, Cdk4 gain plus P16INK4a loss, and Ccnd1 gain plus P16 INK4a loss. Conclusions: Genetic aberration of CDK4 pathway is a frequent event in acral melanoma. Acral melanoma cell lines and PDX containing CDK4 pathway aberrations are sensitive to CDK4/6 inhibitors. Our study provides evidence for the testing of CDK4/6 inhibitors in acral melanoma patients. Clin Cancer Res; 23(22); 6946-57. Ó2017 AACR.