BACKGROUND: The aim of this study was to investigate the prognostic effect of tumour-infiltrating lymphocytes (TILs) in serous stage III ovarian carcinoma to determine TIL clonality and to correlate this to Her2/neu expression. METHODS: Formalin-fixed and paraffin-embedded ovarian carcinomas were examined for CD20-, CD3-, CD4-and CD8-positive lymphocytes (n ¼ 100), and for Her2/neu-positive tumour cells (n ¼ 55/100) by immunohistochemistry. Clonality analysis was carried out by T-cell receptor g (TCRg) gene rearrangements (n ¼ 93/100). Statistical analyses included experimental and clinico-pathological variables, as well as disease-free (DFS) and overall (OS) survival. RESULTS: CD20-positive B lymphocytes were present in 57.7% (stromal)/33.0% (intraepithelial) and CD3-positive T lymphocytes in 99.0% (stromal)/90.2% (intraepithelial) of ovarian carcinomas. Intraepithelial CD3-positive T lymphocytes were correlated with improved DFS in optimally debulked patients (P ¼ 0.0402). Intraepithelial CD8-positive T lymphocytes were correlated with improved OS in all optimally debulked patients (P ¼ 0.0201) and in those undergoing paclitaxel/carboplatin therapy (P ¼ 0.0092). Finally, rarified and clonal TCRg gene rearrangements were detected in 37 out of 93 (39.8%) and 15 out of 93 (16.1%) cases, respectively. This was marginally associated with improved DFS (P ¼ 0.0873). Despite a significant correlation of HER2/neu status and intraepithelial CD8-positive lymphocytes (P ¼ 0.0264), this was non-directional (R ¼ À0.257; P ¼ 0.0626). CONCLUSION: Improved survival of ovarian cancer patients is related to the infiltration, clonal selection and intraepithelial persistence of T lymphocytes.

Aberrant activation of NOTCH1 signaling plays a vital role in the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL). Yet the molecular events downstream of NOTCH1 that drive T-cell leukemogenesis remain incompletely understood. Starting from genome-wide gene-expression profiling to seek important NOTCH1 transcriptional targets, we identified DEP-domain containing mTOR-interacting protein (DEPTOR), which was previously shown to be important in multiple myeloma but remains functionally unclear in other hematological malignancies. Mechanistically, we demonstrated NOTCH1 directly bound to and activated the human DEPTOR promoter in T-ALL cells. DEPTOR depletion abolished cellular proliferation, attenuated glycolytic metabolism and enhanced cell death, while ectopically expressed DEPTOR significantly promoted cell growth and glycolysis. We further showed that DEPTOR depletion inhibited while its overexpression enhanced AKT activation in T-ALL cells. Importantly, AKT inhibition completely abrogated DEPTOR-mediated cell growth advantages. Moreover, DEPTOR depletion in a human T-ALL xenograft model significantly delayed T-ALL onset and caused a substantial decrease of AKT activation in leukemic blasts. We thus reveal a novel mechanism involved in NOTCH1-driven leukemogenesis, identifying the transcriptional control of DEPTOR and its regulation of AKT as additional key elements of the leukemogenic program activated by NOTCH1.

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The two-photon transition c ð3686Þ ! J=c is studied in a sample of 1:06 Â 10 8 c ð3686Þ decays collected by the BESIII detector. The branching fraction is measured to be ð3:1 AE 0:6ðstatÞ þ0:8 À1:0 ðsystÞÞ Â 10 À4 using J=c ! e þ e À and J=c ! þ À decays, and its upper limit is estimated to be 4:5 Â 10 À4 at the 90% confidence level. This work represents the first measurement of a two-photon transition among charmonium states. The orientation of the c ð3686Þ decay plane and the J=c polarization in this decay are also studied. In addition, the product branching fractions of sequential E1 transitions c ð3686Þ ! cJ and cJ ! J=c ðJ ¼ 0; 1; 2Þ are reported. DOI: 10.1103/PhysRevLett.109.172002 PACS numbers: 14.40.Pq, 13.20.Gd The XYZ [1] particles, which do not fit potential model expectations in QCD theory, have been a key challenge to the QCD description of charmoniumlike states [2]. To fully understand those states, it is necessary to consider the coupling of a charmonium state to a D " D meson pair. These coupled-channel effects, which also play an important role in the charmonium transitions of low-lying states [i.e., from c ð3686Þ to J=c ], are especially relevant for the radiative transition processes [3]. In the well-known electric dipole transitions, the strength of coupled-channel effects will likely be hard to establish, since the accompanying relativistic corrections may be more important [4]. However, the two-photon transition c ð3686Þ ! J=c is more sensitive to the coupled-channel effect and thus provides a unique opportunity to investigate these issues [5].Two-photon spectroscopy has been a very powerful tool for the study of the excitation spectra of a variety of PRL 109, 172002 (2012) P H Y S I C A L R E V I E W L E T T E R S week ending 26 OCTOBER 2012172002-2 systems with a wide range of sizes, such as molecules, atomic hydrogen, and positronium [6]. Studying the analogous process in quarkonium states is a natural extension of this work, in order to gain insight into nonperturbative QCD phenomena. But, so far, two-photon transitions in quarkonia have eluded experimental observation [7][8][9]. For example, in a study of c ð3686Þ ! cJ ðJ ¼ 0; 1; 2Þ reported by the CLEO Collaboration [9], the upper limit for Bðc ð3686Þ ! J=c Þ was estimated to be 1 Â 10 À3 . This Letter presents the first evidence for the two-photon transition c ð3686Þ ! J=c , as well as studies of the orientation of the c ð3686Þ decay plane and the J=c polarization in the decay. The branching fractions of double E1 transitions c ð3686Þ ! ðJ=c Þ cJ through cJ intermediate states are also reported. The upgraded BEPCII [12] at Beijing is a two-ring electron-positron collider. The BESIII detector [10] is an approximately cylindrically symmetric detector which covers 93% of the solid angle around the collision point. In the order of increasing distance from the interaction point, the subdetectors include a 43-layer main wire drift chamber (MDC), a time-of-flight system with two layers in the barrel region and one layer for each end c...