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This corrects the article DOI: 10.1038/ncomms15870 [ABSTRACT FROM AUTHOR]

Abstract: Although the importance of B cells in the host immune response upon Mycobacterium tuberculosis infection has been recognized, a conclusive role for B cells has yet to be determined. In the present study, we found that primary CD19+ B cells isolated from patients with tuberculosis significantly inhibited Th17, but not Th1, cell activation. Moreover, the suppressive activity was mediated by a CD19+CD1d+CD5+ B cell population. Notably, patients with tuberculosis were found to have significantly higher frequencies of CD19+CD1d+CD5+ B cells with stronger suppressive activity than such cells from healthy donors. Furthermore, the frequency of CD19+CD1d+CD5+ B cells in peripheral blood was inversely correlated with that of Th17 cells in patients with tuberculosis. This finding that B cells negatively regulate Th17 responses provides a novel mechanism in the regulation of CD4+ T cell responses—aside from regulatory T cells—during M. tuberculosis infection, which may impact the clinical outcome of tuberculosis. [Copyright &y& Elsevier]

We report the synthesis and characterization of novel pentamethylcyclopentadienyl (Cp*) iridium(III) complexes [(Cp*)Ir(4-methyl-4'-carboxy-2,2'-bipyridine)Cl]PF6 (Ir-I), the product (Ir-II) from amide coupling of Ir-I to dibenzocyclooctyne-amine, and its conjugate (Ir-CP) with the cyclic nona-peptide c(CRWYDENAC). The familiar three-legged 'piano-stool' configuration for complex Ir-I was confirmed by its single crystal X-ray structure. Significantly, copper-free click strategy has been developed for site-specific conjugation of the parent complex Ir-I to the tumour targeting nona-cyclic peptide. The approach consisted of two steps: (i) the carboxylic acid group of the bipyridine ligand in complex Ir-I was first attached to an amine functionalized dibenzocyclooctyne group via amide formation to generate complex Ir-II; and (ii) the alkyne bond of dibenzocyclooctyne in complex Ir-II underwent a subsequent strain-promoted copper-free cycloaddition with the azide group of the modified peptide. Interestingly, while complex Ir-I was inactive towards A2780 human ovarian cancer cells, complex Ir-II exhibited moderate cytotoxic activity. Targeted complexes such as Ir-CP offer scope for enhanced activity and selectivity of this class of anticancer complexes., Competing Interests: Declaration of Competing Interest Cyclic peptide is the subject of US patent US9809622B2.

Objective: To elucidate the role and prognostic significance of lymphocyte activation-gene-3 (LAG-3) in soft tissue sarcoma (STS)., Methods: The expression of LAG-3 in patient and matched normal blood samples was analyzed by flow cytometry. The localization and prognostic values of LAG-3 + cells in 163 STS patients were analyzed by immunohistochemistry. In addition, the expression of tumor-infiltrating CD3 + T, CD4 + T, and CD8 + T cells and their role in the prognosis of STS were evaluated by immunohistochemistry. The effect of LAG-3 blockade was evaluated in an immunocompetent MCA205 fibrosarcoma mouse model., Results: Peripheral CD8 + and CD4 + T cells from STS patients expressed higher levels of LAG-3 than those from healthy donors. LAG-3 expression in STS was significantly associated with a poor clinical outcome ( P = 0.038 ) and was correlated with high pathological grade ( P < 0.001), advanced tumor stage ( P = 0.016). Additionally, LAG-3 expression was highly correlated with CD8 + T-cell infiltration ( r = 0.7034, P < 0.001). LAG-3 was expressed in murine tumor-infiltrating lymphocytes, and its blockade decreased tumor growth and enhanced secretion of interferon-gamma by CD8 + and CD4 + T cells., Conclusions: LAG-3 blockade may be a promising strategy to improve the effects of targeted therapy in STS.

The high prevalence and poor prognosis of breast cancer provides a strong rationale for developing new treatment strategies and preventive and therapeutic agents. Oncolytic replication-competent herpes simplex virus (HSV) can infect tumor cells, replicating and killing the cells by direct cytopathic effect and then spreading within the tumor. Replication of oncolytic HSV leads to the destruction of the infected tumor cell and release of new virions, which are able to infect adjacent cells until potentially all tumor cells are destroyed. In this study, the cytotoxicity of a third-generation oncolytic HSV vector, designated G47Δ, was examined in human breast cancer cell lines, as well as in immortalized and normal breast cells. A pulmonary metastatic model of breast cancer established in Balb/c nude mice was used to evaluate the efficacy of G47Δ treatment. Systemic treatment by intravenous administration of G47Δ for metastatic lung tumors was initiated 14 days after injection of tumor cells. On Day 56, the mice were sacrificed and tumor nodules on the surface of the lung were counted. G47Δ was highly cytotoxic to breast cancer and immortalized breast cells in vitro at low multiplicities of infection (MOI), while normal breast cells remained viable 5 days after infection. In the pulmonary metastatic model, the average number of surface lung tumor nodules in the G47Δ-treated group was approximately 9‑fold less than in the control-treated group. X-gal staining illustrated viral replication and spread in the tumor cells in vitro and in vivo. In conclusion, G47Δ effectively killed human breast cancer cells and immortalized breast cells but not normal breast cells. Systemic administration of G47Δ by tail vein injection was effective in inhibiting the growth of established breast cancer lung metastases.

One of the features of malignant gliomas is their deviant resistance to cellular apoptosis induced by cytotoxic reagents. Bmi-1, an oncoprotein, has been linked to oncogenesis and cancer progression in various types of human cancers including gliomas. However, the mechanisms underlying Bmi-1 antiapoptotic function remain largely unknown. In this study, we report that Bmi-1 renders apoptotic resistance to glioma cells through nuclear factor-kappaB (NF-kappaB). In glioma cells, ectopic expression of Bmi-1 significantly inhibits doxorubicin-, BCNU-, or UV irradiation- induced apoptosis through reduction of activated caspase-3 and PARP, and induction of Bcl-X(L). Cellular depletion of Bmi-1 enhances the sensitivity of glioma cells to apoptosis induced by doxorubicin, BCNU, or UV irradiation. Bmi-1 activates NF-kappaB through stimulation of IkappaB phosphorylation, nuclear translocation, and transcriptional activity of NF-kappaB and expression of downstream genes of NF-kappaB including caspase-3, PARP, Bcl-X(L), and c-Myc. Inhibition of the IKK-NF-kappaB pathway abrogates the antiapoptotic effect of Bmi-1 on glioma cells. In high-grade gliomas, Bmi-1 and NF-kappaB are co-expressed in the cell nucleus. Up-regulation of Bmi-1 also correlates with tumor progression and poor survival of patients with gliomas. Together, our data demonstrate that Bmi-1 bestows apoptotic resistance to glioma cells through the IKK-NF-kappaB pathway and suggest Bmi-1 as a useful indicator for glioma prognosis.