Pan-cancer landscape of immunology PIWI-interacting RNAs

PIWI-interacting RNAs (piRNAs), an emergent type of non-coding RNAs during oncogenesis, play critical roles in regulating tumor microenvironment. Systematic analysis of piRNAs’ roles in modulating immune pathways is important for tumor immunotherapy. In this study, in-depth analysis of piRNAs was performed to develop an integrated computational algorithm, the immunology piRNA (ImmPI) pipeline, for uncovering the global expression landscape of piRNAs and identifying their regulatory roles in immune pathways. The immunology piRNAs show a tendency towards overexpression patterns in immune cells, causing perturbations in tumors, being significantly associated with infiltration of immune cells, and having prognostic value. The ImmPI score can contribute to prioritizing tumor-related piRNAs and distinguish two subtypes of SKCM (immune-cold and hot phenotypes), as characterized by different prognoses, immunogenicity and antitumor immunity. Finally, we developed an interactive web resource (ImmPI portal: http://www.hbpding.com/ImmPi) for the biomedical research community, with several useful modules to browse, visualize, and download the results of immunology piRNAs analysis. Overall, our work provides a comprehensive landscape of piRNAs across multiple cancer types and sheds light on their regulatory and functional roles in tumor immunity. These findings pave the way for future research and development of piRNA-based immunotherapies for cancer treatment

IMOPAC: A web server for interactive multiomics and pharmacological analyses of patient-derived cancer cell lines

Large-scale multidimensional cancer genomic and pharmacological profiles have been created by several large consortium projects, including NCI-60, GDSC and DepMap, providing novel opportunities for data mining and further understanding of intrinsic therapeutic response mechanisms. However, it is increasingly challenging for experimental biologists, especially those without a bioinformatic background, to integrate, explore, and analyse these tremendous pharmacogenomics. To address this gap, IMOPAC, an interactive and easy-to-use web-based tool, was introduced to provide rapid visualizations and customizable functionalities on the basis of these three publicly available databases, which may reduce pharmacogenomic profiles from cell lines into readily understandable genetic, epigenetic, transcriptionomic, proteomic, metabolomic, and pharmacological events. The user-friendly query interface together with customized data storage enables users to interactively investigate and visualize multiomics alterations across genes and pathways and to link these alterations with drug responses across cell lines from diverse cancer types. The analyses in our portal include pancancer expression, drug-omics/pathway correlation, cancer subtypes, omics-omics (cis-/trans-regulation) correlation, fusion query analysis, and drug response prediction analysis. The comprehensive multiomics and pharmacogenomic analyses with simple clicking through IMOPAC will significantly benefit cancer precision medicine, contribute to the discoveries of potential biological mechanisms and facilitate pharmacogenomics mining in the identification of clinically actionable biomarkers for both basic researchers and clinical practitioners. IMOPAC is freely available at http://www.hbpding.com/IMOPAC

Evaluated Conjunctival Blood Flow Velocity in Daily Contact Lens Wearers

This study examined conjunctival microvasculature development in long-term habitual contact lens (HCL) wearers after a night of sleep. Twenty HCL wearers (15 women and 5 men, aged 28.6±6.9 years, mean age±standard deviation) who had worn contact lenses on a daily basis for at least 3 years and 40 noncontact lens (NCL) wearers (23 women and 17 men, aged 36.5±6.6 years, mean age±standard deviation) participated in the study. A functional slitlamp biomicroscopy imaging system was used to image the temporal bulbar conjunctiva. Imaging was performed in the morning while the contact lens wearers were not wearing their lenses after a night of sleep. The conjunctival vessel diameters, blood flow velocities, and flow rates were measured. In addition, fractal analyses were performed to obtain the vessel network density (Dbox) and complexity (D0). The average blood flow velocity in HCL wearers after a night of sleep was 0.59±0.19 mm/s, which was significantly higher than that in NCL wearers (0.48±0.17 mm/s, P<0.05). The microvessel network density and complexity levels (Dbox=1.64±0.05 and D0=1.71±0.05, respectively) in the HCL wearers were significantly higher than those in NCL wearers (Dbox=1.61±0.05 and D0=1.69±0.04, both P<0.05). The blood flow velocity was positively correlated with the duration of contact lens wear (r=0.46, P<0.05) and with the daily number of lens-wearing hours (r=0.49, P<0.05) in HCL wearers. This study identified microvascular alterations in the conjunctiva in response to daily contact lens wear after a night of sleep in long-term daily contact lens wearers. The unrecovered changes may indicate that para-inflammation occurs on ocular surfaces because of contact lens wear and that overnight sleeping with no lenses may not sufficiently restore the ocular surface to an intact state

Case Report: Active tuberculosis infection in CAR T-cell recipients post CAR T-cell therapy: a retrospective case series

High response rates in B-cell malignancies have been achieved with chimeric antigen receptor (CAR) T-cell therapy. Emerging reports indicate a risk of active tuberculosis (TB) with novel immunotherapy for tumors. However, studies of TB in patients post CAR T-cell therapy are limited. In this case series study, we describe five patients with active TB post CD19/CD22 target CAR T-cell therapy alone or following autologous stem cell transplantation (ASCT). One of the patients developed active TB within the first 30 days post CAR T-cell therapy, and fever was the dominant presenting symptom; extrapulmonary manifestations of active TB were common in the other four patients and manifested after the first 30 days of CAR T-cell therapy. Four of the five patients improved with anti-TB treatment, but one patient with isoniazid resistance died of central nervous system TB infection. Our study provides the first series report of active TB following CD19/CD22 target CAR T-cell therapy

Prognostic and therapeutic value of disruptor of telomeric silencing-1-like (DOT1L) expression in patients with ovarian cancer

Abstract Background Epigenetics has been known to play a critical role in regulating the malignant phenotype. This study was designed to examine the expression of DOT1L (histone 3 lysine 79 methyltransferase) and H3K79 methylation in normal ovarian tissues and ovarian tumors and to explore the function of DOT1L and its underline mechanisms in ovarian cancer. Methods The expression of DOT1L and H3K79 methylation in 250 ovarian tumor samples and 24 normal ovarian samples was assessed by immunohistochemistry. The effects of DOT1L on cell proliferation in vitro were evaluated using CCK8, colony formation and flow cytometry. The DOT1L-targeted genes were determined using chromatin immune-precipitation coupled with high-throughput sequencing (ChIP-seq) and ChIP-PCR. Gene expression levels were measured by real-time PCR and immunoblotting. The effects of DOT1L on tumor growth in vivo were evaluated using an orthotopic ovarian tumor model. Results DOT1L expression and H3K79 methylation was significantly increased in malignant ovarian tumors. High DOT1L expression was associated with International Federation of Gynecology and Obstetrics (FIGO) stage, histologic grade, and lymphatic metastasis. DOT1L was an independent prognostic factor for the overall survival (OS) and progression-free survival (PFS) of ovarian cancer, and higher DOT1L expression was associated with poorer OS and PFS. Furthermore, DOT1L regulates the transcription of G1 phase genes CDK6 and CCND3 through H3K79 dimethylation; therefore, blocking DOT1L could result in G1 arrest and thereby impede the cell proliferation in vitro and tumor growth in vivo. Conclusions Our findings first demonstrate that DOT1L over-expression has important clinical significance in ovarian cancer and also clarify that it drives cell cycle progression through transcriptional regulation of CDK6 and CCND3 through H3K79 methylation, suggesting that DOT1L might be potential target for prognostic assessment and therapeutic intervention in ovarian cancer