Bacterial infection disrupts established germinal center reactions through monocyte recruitment and impaired metabolic adaptation

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Circulating MicroRNAs and Extracellular Vesicle–Containing MicroRNAs as Response Biomarkers of Anti–programmed Cell Death Protein 1 or Programmed Death-Ligand 1 Therapy in NSCLC

IntroductionAnti–programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) antibody therapy is a standard treatment for advanced NSCLC, and PD-L1 immunohistochemistry is used as a predictive biomarker for therapeutic response. However, because not all patients with NSCLC with high PD-L1 respond, and some patients with low PD-L1 expression exhibit durable benefit, more accurate predictive biomarkers are needed. Circulating microRNA (miRNA) and miRNA packaged in extracellular vesicles (EVs) are believed to play a role in intercellular communication among immune cells and between immune cells and tumor cells and may represent a good source of mechanism-related biomarkers.MethodsPretreatment plasma of patients with advanced NSCLC treated with single-agent anti–PD-1 or anti–PD-L1 antibody was used in this study. Plasma EVs were isolated using size-exclusion chromatography. Whole plasma and EV-containing RNAs were extracted. The miRNA profile was analyzed with a next-generation sequencing platform.ResultsSamples from 14 responders (patients who exhibited partial response or stable disease ≥6 mo) and 15 nonresponders (patients who exhibited progressive disease as per Response Evaluation Criteria in Solid Tumors) were analyzed. In total, 32 miRNAs (p = 0.0030–0.0495) from whole plasma and seven EV-associated miRNAs (p = 0.041–0.0457) exhibited significant concentration differences between responders and nonresponders. The results of some of these circulating miRNAs were validated in a separate cohort with eight responders and 13 nonresponders. The tumor PD-L1 level was also assessed using immunohistochemistry for patients involved in both cohorts.ConclusionsSpecific circulating miRNAs in whole plasma and plasma EVs are differentially expressed between responders and nonresponders and have potential as predictive biomarkers for anti–PD-1/PD-L1 treatment response.     

B cell and B cell-related pathways for novel cancer treatments

B cells are recognized as the main effector cells of humoral immunity which suppress tumor progression by secreting immunoglobulins, promoting T cell response, and killing cancer cells directly. Given these properties, their anti-tumor immune response in the tumor micro-environment (TME) is of great interest. Although T cell-related immune responses have become a therapeutic target with the introduction of immune checkpoint inhibitors, not all patients benefit from these treatments. B cell and B cell-related pathways (CCL19, −21/CCR7 axis and CXCL13/CXCR5 axis) play key roles in activating immune response through humoral immunity and local immune activation via tertiary lymphoid structure (TLS) formation. However they have some protumorigenic works in the TME. Thus, a better understanding of B cell and B cell-related pathways is necessary to develop effective cancer control. In this review, we summarize recent evidences regarding the roles of B cell and B cell-related pathways in the TME and immune response and discuss their potential roles for novel cancer treatment strategies.     

Morphometric analysis of human oocytes using time lapse: does it predict embryo developmental outcomes?

The aim of this prospective study was to evaluate the relationship between morphometric parameters of metaphase II (MII) oocytes and the morphokinetic behaviour of subsequent embryos derived by intra-cytoplasmic sperm injection (ICSI). The association between oocyte morphometry: (whole oocyte), ooplasm, width of zona pellucida (ZP) and perivitelline space (PVS) and first polar body (PB) with embryo morphokinetic variables, including time of second PB extrusion (tPB2), pronuclei appearance (tPN), pronuclei fading (tPNf), formation of two to eight cells (t2 to t8) and irregular cleavage events [uneven at two cells stage, cell fusion (Fu) and trichomonas mitoses (TM)] were assessed. tPB2, t5 and t8 timings were related to the ooplasm diameter (p?=?0.003, r?=??0.12; p?=?0.001, r?=??0.16; p?r?=??0.36, respectively); otherwise, there were no significant relationships apart from an association between the oocyte morphometry and other morphokinetic parameters, irregular cleavage embryos as well as embryo arrest which approached significance (p?>?0.05). Overall, the data showed that morphometric parameters of oocytes did not provide a tool for the prediction of embryo morphokinetic or embryo selection in ICSI cycles. However, ooplasm diameter might be useful as a marker for predicting the timing of embryo cleavage.     

精囊镜技术治疗血精症的临床效果评估

目的评价经自然腔道精囊镜技术治疗血精症的临床效果。方法以广东省江门市中心医院2015年3月-2019年8月收治的20例难治性血精症或保守治疗失败的血精症患者为研究对象,随机分成观察组和对照组各10例,观察组使用自然腔道精囊镜技术,对照组使用破窗法精囊镜技术,比较两组患者的治疗效果。结果观察组患者的治疗有效率为90.00%,高于对照组的70.00%,差异有统计学意义(P<0.05)。观察组并发症发生率为20.00%,对照组为10.00%,两组差异无统计学意义(P>0.05)。结论经自然腔道精囊镜技术治疗血精症具有更好的疗效,且并发症发生率与破窗法无明显差异,提示经自然腔道精囊镜技术更加安全有效,值得临床推广应用。     

Epstein‐Barr virus‐encoded latent membrane protein 1 promotes extracellular vesicle secretion through syndecan‐2 and synaptotagmin‐like‐4 in nasopharyngeal carcinoma cells

Increasing evidence indicates that extracellular vesicles (EVs) play an important role in cancer cell‐to‐cell communication. The Epstein‐Barr virus (EBV)‐encoded latent membrane protein 1 (LMP1), which is closely associated with nasopharyngeal carcinoma (NPC) pathogenesis, can trigger multiple cell signaling pathways that affect cell progression. Several reports have shown that LMP1 promotes EV secretion, and LMP1 trafficking by EVs can enhances cancer progression and metastasis. However, the molecular mechanism by which LMP1 promotes EV secretion is not well understood. In the present study, we found that LMP1 promotes EV secretion by upregulated syndecan‐2 (SDC2) and synaptotagmin‐like‐4 (SYTL4) through nuclear factor (NF)‐κB signaling in NPC cells. Further study indicated that SDC2 interacted with syntenin, which promoted the formation of the EVs, and SYTL4 is associated with the release of EVs. Moreover, we found that stimulation of EV secretion by LMP1 can enhance the proliferation and invasion ability of recipient NPC cells and tumor growth in vivo. In summary, we found a new mechanism by which LMP1 upregulates SDC2 and SYTL4 through NF‐κB signaling to promote EV secretion, and further enhance cancer progression of NPC.