Expression of PD-L1 on Monocytes Is a Novel Predictor of Prognosis in Natural Killer/T-Cell Lymphoma.

Background: Natural killer/T-cell lymphoma (NKTCL) is a highly aggressive lymphoma with a dismal prognosis, and novel therapeutic targets are urgently needed. Programmed death-ligand 1 (PD-L1) has become a promising therapeutic target for various cancers, but most of the studies have focused on expression of PD-L1 on tumor cells. Expression of PD-L1 on tumor-infiltrating non-malignant cells, especially monocytes, has not been studied in NKTCL, and its prognostic value remains unknown. Materials and Methods: Expression of PD-L1 on tumor-infiltrating stromal cells was measured in NKTert and HS5 cells when cultured alone or co-cultured with NKTCL cell lines. Clinical samples were collected from 42 patients with newly diagnosed NKTCL. Expression of PD-L1 on monocytes was analyzed in patients' peripheral blood and tumor tissues using flow cytometry and immunofluorescent staining, respectively. Survival data were retrospectively collected and the prognostic significance of PD-L1 expression on monocytes was analyzed. Results: PD-L1 expression on tumor-infiltrating stromal cells was remarkably elevated when co-cultured with NKTCL cells. The percentage of PD-L1+ monocytes among all monocytes in peripheral blood was significantly higher in NKTCL patients than that in healthy individuals. Among NKTCL patients, percentage of PD-L1+ monocytes in blood positively correlated with that in tumor tissues. Patients with a higher percentage (≥78.2%) of PD-L1+ monocytes in blood or with a higher percentage (≥24.2%) of PD-L1+ monocytes in tumor tissues exhibited a significantly inferior survival, compared with their counterparts. A higher percentage of PD-L1+ monocytes in blood or tumor tissues was an independent adverse prognostic factor. Conclusions: Expression of PD-L1 on monocytes is up-regulated and has significant prognostic value in patients with NKTCL.

Characteristics, Prognostic Factors, and Survival of Patients with NK/T-Cell Lymphoma of Non-upper Aerodigestive Tract: A 17-Year Single-Center Experience.

PURPOSE: The extranodal natural killer (NK)/T-cell lymphoma (NKTCL) of non-upper aerodigestive tract (NUAT) was found to have clinical heterogeneity compared with NKTCL of the upper aerodigestive tract (UAT) in small scale studies. We conducted this study in a much larger cohort to analyze the clinical characteristics, prognostic factors, treatment modality, and clinical outcomes of patients with NUAT-NKTCL. MATERIALS AND METHODS: From January 2001 to December 2017, a total of 757 NKTCL patients were identified and included in this study, including 92 NUAT-NKTCL patients (12.2%) and 665 UAT-NKTCL patients (87.8%). RESULTS: NUAT-NKTCL patients had relatively poorer performance status, more unfavorable prognostic factors, and more advanced stage, compared with UAT-NKTCL patients. The 5-year overall survival (OS) was 34.7% for NUAT-NKTCL, which was significantly worse than UAT-NKTCL (64.2%, p<0.001). The median OS duration was 30.9 months for NUAT-NKTCL. Multivariate analysis showed that presence with B symptoms and elevated serum lactate dehydrogenase independently predicted worse OS. International prognostic index score and prognostic index of natural killer lymphoma score still had prognostic values in NUAT-NKTCL, while the Ann Arbor system could not accurately predict the OS. CONCLUSION: NUAT-NKTCL is a distinctive subtype of NKTCL in many aspects. Patients with NUAT-NKTCL have relatively poorer performance status, more unfavorable prognostic factors, more advanced stage, and poorer prognosis.

Trends in survival of patients with stage I/II Burkitt lymphoma in the United States: A SEER database analysis.

The treatment strategy for management of Burkitt lymphoma (BL) has evolved during the past decades and the clinical outcome for this disease as a whole has also improved. Due to limited information reported on survival trends of patients with stage I/II (limited-stage) BL, here we used the Surveillance, Epidemiology, and End Results (SEER) database to conduct our study. The time period was divided into two eras (1983-2001 and 2002-2014) as the recent era reflected more intensive chemotherapy regimens, the availability of rituximab, the widespread use of antiretroviral therapy (ART) and improvements in supportive care. Patients with limited-stage BL had a significantly better 5-year overall survival (OS) in the 2002-2014 era in both univariate analysis and multivariate analysis, compared with those in the 1983-2001 era (64.1% vs 57.4%). However, clinical outcomes of elderly patients (≥60 years) and children patients (0-19 years) did not significantly improve. Older age and race of black were correlated with poorer OS in multivariate analysis, whereas sex, primary sites, and application of radiotherapy did not significantly influence OS. In conclusion, the prognosis of patients with limited-stage BL has improved in the 2002-2014 era, but the outcome was still much poorer in elderly patients, which needs to be improved by identifying newly molecular-targeted drugs and developing novel personalized therapeutic approaches.

The Clinical Utility of Circulating Epstein-Barr Virus DNA Concentrations in NK/T-Cell Lymphoma: A Meta-Analysis.

BACKGROUND: Circulating Epstein-Barr virus (EBV) DNA concentrations were reported to have prognostic value for NK/T-cell lymphoma patients in limited small-scale studies. In this study, we aimed to evaluate the clinical utility of circulating EBV-DNA concentrations to a large sample of NK/T-cell lymphoma patients. METHODS: We conducted this meta-analysis, which included a total of 15 prospective and retrospective comparable studies to assess the association between pretreatment EBV-DNA (pre-DNA), posttreatment EBV-DNA (post-DNA), and clinical outcomes of NK/T-cell lymphoma patients. We chose overall survival (OS) as the primary endpoint and progression-free survival (PFS), complete response (CR), and overall response rate (ORR) as secondary endpoints. RESULTS: High pre-DNA and detectable post-DNA were both significantly correlated with poorer OS in NK/T-cell lymphoma patients (P < 0.05), with hazard radios (HRs) equal to 3.45 and 2.30, respectively. High pre-DNA and detectable post-DNA also predicted poorer PFS. Additionally, high pre-DNA was found to be significantly correlated with both worse CR and ORR, which indicated worse treatment response. CONCLUSION: Circulating EBV-DNA concentrations provides prognostic values of survival and treatment response in NK/T-cell lymphoma patients.

Expressions and prognostic values of the E2F transcription factors in human breast carcinoma.

E2F transcription factors (E2Fs) are a family of transcription factors involved in cell proliferation, differentiation, and apoptosis. Their important roles in the development and metastasis of breast carcinoma (BC) have been discovered by previous in vitro and in vivo studies. Yet, expressions and distinct prognostic values of these eight E2Fs in human BC remain unclear in many respects. In this study, we aimed to reveal their roles in BC through analyzing the transcription and survival data of the E2Fs in BC patients from four online databases including ONCOMINE, Breast Cancer Gene-Expression Miner v4.1, cBioPortal for Cancer Genomics, and Kaplan-Meier Plotter. We found the overexpression of E2Fs in BC tissues compared with normal breast tissues, except for E2F4. Higher expression levels of E2Fs, except for E2F4 and E2F6, were associated with higher levels of Scarff-Bloom-Richardson grade of BC. Alterations of E2Fs were found to be significantly correlated with poorer overall survival of BC patients. Through plotting the survival curve in the Kaplan-Meier Plotter, it was found that higher mRNA levels of E2F1, E2F3, E2F7, and E2F8 were associated with poorer relapse-free survival in all BC patients, indicating that they are potential targets for individualized treatments of BC patients. Conversely, higher mRNA expression level of E2F4 predicted better RFS in BC patients, suggesting E2F4 as a new biomarker for BC prognosis. Considering currently available limited evidence, further studies need to be performed to investigate the roles of E2Fs in BC.