A preliminary study: The sequential use of the risk malignancy index and contrast-enhanced ultrasonography in differential diagnosis of adnexal masses.

Regulation and Function of the PD-L1 Checkpoint

Cancer immunotherapy has been accompanied by promising results over the past few years. Programmed Cell Death Protein 1 (PD-1) plays a vital role in inhibiting immune responses and promoting self-tolerance through modulating the activity of T-cells, activating apoptosis of antigen-specific T cells and inhibiting apoptosis of regulatory T cells. Programmed Cell Death Ligand 1 (PD-L1) is a trans-membrane protein that is considered to be a co-inhibitory factor of the immune response, it can combine with PD-1 to reduce the proliferation of PD-1 positive cells, inhibit their cytokine secretion and induce apoptosis. PD-L1 also plays an important role in various malignancies where it can attenuate the host immune response to tumor cells. Based on these perspectives, PD-1/PD-L1 axis is responsible for cancer immune escape and makes a huge effect on cancer therapy. This review is aimed to summarize the role of PD-1 and PD-L1 in cancer, looking forward to improve the therapy of cancer.

PD-1/PD-L1 pathway: current researches in cancer

We herein present an overview of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms. 

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The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms

The protein tyrosine phosphatase (Ptp) family dephosphorylates target proteins and counters the activities of protein tyrosine kinases. Accumulating evidence indicates that some PTPs have an important role in the inhibition or control of growth, whereas some PTPs exert oncogenic functions. This Review discusses the relevance of PTPs to cancer biology and their potential as therapeutic targets.

Inside the human cancer tyrosine phosphatome

Natural killer/T-cell lymphoma (NKTCL) is an Epstein–Barr virus (EBV)-associated, highly aggressive lymphoma. Treatment outcome remains sub-optimal, especially for advanced-stage or relapsed diseases. Programmed cell death receptor 1 (PD-1) and PD ligand 1 (PD-L1) have become promising therapeutic targets for various malignancies, but their role in the pathogenesis and their interactions with EBV in NKTCL remains to be investigated. Expression of PD-L1 was measured in NK-92 (EBV-negative) and SNK-6 (EBV-positive) cells by western blot, quantitative real-time PCR and enzyme-linked immunosorbent assay, and flow cytometry, respectively. Latent membrane protein 1 (LMP1)-harboring lentiviral vectors were transfected into NK-92 cells to examine the correlation between LMP1 and PD-L1 expression. Proteins in the downstream pathways of LMP1 signaling were measured in NK-92 cells transfected with LMP1-harboring or negative control vectors as well as in SNK-6 cells. PD-L1 expression on tumor specimens and serum concentration of soluble PD-L1 were collected in a retrospective cohort of patients with Ann Arbor stage I~II NKTCL, and their prognostic significance were analyzed. Expression of PD-L1 was significantly higher in SNK-6 cells than in NK-92 cells, at both protein and mRNA levels. Expression of PD-L1 was remarkably upregulated in NK-92 cells transfected with LMP1-harboring lentiviral vectors compared with those transfected with negative control vectors. Proteins in the MAPK/NF-κB pathway were upregulated in LMP1-expressing NK-92 cells compared with the negative control. Selective inhibitors of those proteins induced significant downregulation of PD-L1 expression in LMP1-expressing NK-92 cells as well as in SNK-6 cells. Patients with a high concentration of serum soluble PD-L1 (≥3.4 ng/ml) or with a high percentage of PD-L1 expression in tumor specimens (≥38 %) exhibited significantly lower response rate to treatment and remarkably worse survival, compared with their counterparts. A high concentration of serum soluble PD-L1 and a high percentage of PD-L1 expression in tumor specimens were independent adverse prognostic factors among patients with stage I~II NKTCL. PD-L1 expression positively correlated LMP1 expression in NKTCL, which was probably mediated by the MAPK/NF-κB pathway. PD-L1 expression in serum and tumor tissues has significant prognostic value for early-stage NKTCL.

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PD-L1 is upregulated by EBV-driven LMP1 through NF-κB pathway and correlates with poor prognosis in natural killer/T-cell lymphoma

// Liang Wang 1, 2, * , Hua Wang 1, 2, * , Hao Chen 1, 3, * , Wei-da Wang 1, 2 , Xiao-qin Chen 1, 2 , Qi-rong Geng 1, 2 , Zhong-jun Xia 1, 2 , Yue Lu 1, 2 1 State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, People’s Republic of China 2 Department of Hematologic Oncology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China 3 Department of Clinical Laboratory, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China * These authors have contributed equally to this work Correspondence to: Yue Lu, e-mail: luyuesysucc@126.com Keywords: multiple myeloma, programmed death-ligand 1, immune checkpoint, prognosis, biomarker Received: May 31, 2015      Accepted: September 13, 2015      Published: October 16, 2015 ABSTRACT Immune checkpoint signaling plays an important role in immunosuppression in multiple myeloma (MM). Blood levels of soluble programmed death-ligand 1 (sPD-L1), a checkpoint-relevant protein, might predict treatment response and survival outcomes in MM patients. We used an enzyme-linked immunosorbent assay to measure serum sPD-L1 levels in 81 newly diagnosed MM patients. We found that myeloma patients had higher sPD-L1 concentrations than healthy controls. The best sPD-L1 cutoff value for predicting disease progression risk was 2.783 ng/mL. The overall response rate to treatment was higher in low sPD-L1 patients than in high sPD-L1 patients. The 3-year progression free survival (PFS) and overall survival (OS) rates for all patients were 16% and 64%, respectively. Multivariate survival analysis including Eastern Cooperative Oncology Group performance status score, treatment response, and sPD-L1 level showed that a less than partial treatment response (PR) and higher sPD-L1 levels (>2.783 ng/ml) were independent prognostic factors for shorter PFS; neither factor was predictive of OS. The serum sPD-L1 level is a valuable biomarker for predicting treatment response and an independent prognostic factor for PFS. PD-1/ PD-L1 blockade may be a promising novel immune-based therapeutic strategy in MM.

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Serum levels of soluble programmed death ligand 1 predict treatment response and progression free survival in multiple myeloma

// Liang Wang 1, * , Zhenxian Zhao 2, * , Weidong Feng 1, * , Zhijun Ye 1 , Weigang Dai 1 , Changhua Zhang 1 , Jianjun Peng 1 , Kaiming Wu 1 1 Department of Gastrointestinal Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China 2 Department of Biliary Pancreatic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China * These authors contributed equally to this work Correspondence to: Kaiming Wu, email: drkaimingwu@163.com Keywords: long noncoding RNA,TUG1, CRC, EMT Received: March 04, 2016      Accepted: May 19, 2016      Published: July 13, 2016 ABSTRACT Colorectal cancer (CRC) is the third most common malignancy in developed countries, and its incidence rate has been continuously increasing in developing countries over the past few decades. Taurine-upregulated gene 1 (TUG1) plays an important role in signal transduction, regulation of cell morphology, migration, proliferation and apoptosis. The aim of the present study was to evaluate the role of TUG1 in CRC, and whether knockdown of TUG1 expression could affect cell proliferation, migration and invasion of CRC cell lines. Here, we reported that TUG1 was upregulated in CRC. Further experiments revealed that TUG1 knockdown significantly inhibited cell proliferation, migration and invasion of CRC in vitro . Above all, knockdown of TUG1 may represent a rational therapeutic strategy for CRC patients in future.

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Long non-coding RNA TUG1 promotes colorectal cancer metastasis via EMT pathway

No standard chemotherapy regimens have been defined yet for extranodal natural killer/T cell lymphoma (ENKTL), and the prognosis of patients with advanced or relapsed disease is very poor. Daratumumab, an investigated anti-cancer drug targeting CD38, has been of great interest in the treatment of CD38-expressing malignancies, especially multiple myeloma. In this study, we reviewed the clinical data of 94 patients with ENKTL, investigated the expression of CD38, and analyzed the prognostic value of CD38 expression. Forty-seven patients had weak expression of CD38, and the other 47 patients had strong expression. The complete response (CR) rate was significantly higher in patients who were treated with asparaginase-based therapy (83.8 vs. 59.6 %, p = 0.025). There was a trend towards higher CR rate in CD38 weak expression group (78.7 vs. 59.6 %, p = 0.074). At a median follow-up time of 42 months, the 2-year and 5-year progression-free survival (PFS) rates were 53.0 and 39.0 %, respectively, and the 2-year and 5-year overall survival (OS) rates were 68.0 and 58.0 %, respectively. In multivariate survival analysis including CD38 expression status, International Prognostic Index (IPI) score, local tumor invasion, and chemotherapy regimens, it was found that strong expression of CD38 and non-asparaginase-based chemoregimens were independent adverse prognostic factors for PFS (p = 0.009 and 0.027, respectively), while local tumor invasion and higher IPI score were independent adverse prognostic factors for OS (p = 0.002 and 0.035, respectively). In subgroup analysis, strong expression of CD38 significantly correlated with inferior survival outcomes in patients without local tumor invasion (p = 0.011) or with stage I–II disease (p = 0.008). In conclusion, we firstly found that the majority of ENKTL cases were CD38 positive, with half had strong expression of CD38, which significantly correlated with poor outcomes, indicating the potential role of CD38 as a therapy target for ENKTL.

Liang Wang

Papers

PD-L1 is upregulated by EBV-driven LMP1 through NF-κB pathway and correlates with poor prognosis in natural killer/T-cell lymphoma

Serum levels of soluble programmed death ligand 1 predict treatment response and progression free survival in multiple myeloma

Long non-coding RNA TUG1 promotes colorectal cancer metastasis via EMT pathway

CD38 expression predicts poor prognosis and might be a potential therapy target in extranodal NK/T cell lymphoma, nasal type

Risk Factor Profiles Differ for Cancers of Different Regions of the Colorectum