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      Tumor immune microenvironment lncRNAs

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          Abstract

          Long non-coding ribonucleic acids (RNAs) (lncRNAs) are key players in tumorigenesis and immune responses. The nature of their cell type-specific gene expression and other functional evidence support the idea that lncRNAs have distinct cellular functions in the tumor immune microenvironment (TIME). To date, the majority of lncRNA studies have heavily relied on bulk RNA-sequencing data in which various cell types contribute to an averaged signal, limiting the discovery of cell type-specific lncRNA functions. Single-cell RNA-sequencing (scRNA-seq) is a potential solution for tackling this limitation despite the lack of annotations for low abundance yet cell type-specific lncRNAs. Hence, updated annotations and further understanding of the cellular expression of lncRNAs will be necessary for characterizing cell type-specific functions of lncRNA genes in the TIME. In this review, we discuss lncRNAs that are specifically expressed in tumor and immune cells, summarize the regulatory functions of the lncRNAs at the cell type level and highlight how a scRNA-seq approach can help to study the cell type-specific functions of TIME lncRNAs.

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          Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.

          Blockade of programmed death 1 (PD-1), an inhibitory receptor expressed by T cells, can overcome immune resistance. We assessed the antitumor activity and safety of BMS-936558, an antibody that specifically blocks PD-1. We enrolled patients with advanced melanoma, non-small-cell lung cancer, castration-resistant prostate cancer, or renal-cell or colorectal cancer to receive anti-PD-1 antibody at a dose of 0.1 to 10.0 mg per kilogram of body weight every 2 weeks. Response was assessed after each 8-week treatment cycle. Patients received up to 12 cycles until disease progression or a complete response occurred. A total of 296 patients received treatment through February 24, 2012. Grade 3 or 4 drug-related adverse events occurred in 14% of patients; there were three deaths from pulmonary toxicity. No maximum tolerated dose was defined. Adverse events consistent with immune-related causes were observed. Among 236 patients in whom response could be evaluated, objective responses (complete or partial responses) were observed in those with non-small-cell lung cancer, melanoma, or renal-cell cancer. Cumulative response rates (all doses) were 18% among patients with non-small-cell lung cancer (14 of 76 patients), 28% among patients with melanoma (26 of 94 patients), and 27% among patients with renal-cell cancer (9 of 33 patients). Responses were durable; 20 of 31 responses lasted 1 year or more in patients with 1 year or more of follow-up. To assess the role of intratumoral PD-1 ligand (PD-L1) expression in the modulation of the PD-1-PD-L1 pathway, immunohistochemical analysis was performed on pretreatment tumor specimens obtained from 42 patients. Of 17 patients with PD-L1-negative tumors, none had an objective response; 9 of 25 patients (36%) with PD-L1-positive tumors had an objective response (P=0.006). Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non-small-cell lung cancer, melanoma, or renal-cell cancer; the adverse-event profile does not appear to preclude its use. Preliminary data suggest a relationship between PD-L1 expression on tumor cells and objective response. (Funded by Bristol-Myers Squibb and others; ClinicalTrials.gov number, NCT00730639.).
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            Understanding the tumor immune microenvironment (TIME) for effective therapy

            The clinical successes in immunotherapy have been both astounding and at the same time unsatisfactory. Countless patients with varied tumor types have seen pronounced clinical response with immunotherapeutic intervention; however, many more patients have experienced minimal or no clinical benefit when provided the same treatment. As technology has advanced, so has the understanding of the complexity and diversity of the immune context of the tumor microenvironment and its influence on response to therapy. It has been possible to identify different subclasses of immune environment that have an influence on tumor initiation and response and therapy; by parsing the unique classes and subclasses of tumor immune microenvironment (TIME) that exist within a patient’s tumor, the ability to predict and guide immunotherapeutic responsiveness will improve, and new therapeutic targets will be revealed.
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              Massively parallel digital transcriptional profiling of single cells

              Characterizing the transcriptome of individual cells is fundamental to understanding complex biological systems. We describe a droplet-based system that enables 3′ mRNA counting of tens of thousands of single cells per sample. Cell encapsulation, of up to 8 samples at a time, takes place in ∼6 min, with ∼50% cell capture efficiency. To demonstrate the system's technical performance, we collected transcriptome data from ∼250k single cells across 29 samples. We validated the sensitivity of the system and its ability to detect rare populations using cell lines and synthetic RNAs. We profiled 68k peripheral blood mononuclear cells to demonstrate the system's ability to characterize large immune populations. Finally, we used sequence variation in the transcriptome data to determine host and donor chimerism at single-cell resolution from bone marrow mononuclear cells isolated from transplant patients.
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                Author and article information

                Contributors
                Journal
                Brief Bioinform
                Brief Bioinform
                bib
                Briefings in Bioinformatics
                Oxford University Press
                1467-5463
                1477-4054
                January 2022
                10 December 2021
                10 December 2021
                : 23
                : 1
                : bbab504
                Affiliations
                Department of Life Science, College of Natural Sciences, Hanyang University , Seoul 04763, Republic of Korea
                Department of Life Science, College of Natural Sciences, Hanyang University , Seoul 04763, Republic of Korea
                Department of Life Science, College of Natural Sciences, Hanyang University , Seoul 04763, Republic of Korea
                Department of Life Science, College of Natural Sciences, Hanyang University , Seoul 04763, Republic of Korea
                Department of Life Science, College of Natural Sciences, Hanyang University , Seoul 04763, Republic of Korea
                Research Institute for Convergence of Basic Sciences, Hanyang University , Seoul 04763, Republic of Korea
                Research Institute for Natural Sciences, Hanyang University , Seoul 04763, Republic of Korea
                Author notes
                Corresponding author: Jin-Wu Nam, Department of Life Science, College of Nature Sciences, Hanyang University, Seoul 04763, Republic of Korea. Tel: +82-2-2220-2428; Fax: +82-2-2298-0319; E-mail: jwnam@ 123456hanyang.ac.kr

                Eun-Gyeong Park, Sung-Jin Pyo, Youxi Cui, Sang-Ho Yoon contributed equally to this work.

                Author information
                https://orcid.org/0000-0003-2611-5554
                https://orcid.org/0000-0003-0047-3687
                Article
                bbab504
                10.1093/bib/bbab504
                8769899
                34891154
                6618269c-ea75-4df0-8c91-b20aba0cd07c
                © The Author(s) 2021. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 20 August 2021
                : 15 October 2021
                : 2 November 2021
                Page count
                Pages: 25
                Funding
                Funded by: National Research Foundation of Korea, DOI 10.13039/501100003725;
                Award ID: 2020R1A4A1018398
                Award ID: 2021R1A2C3005835
                Categories
                Review
                AcademicSubjects/SCI01060

                Bioinformatics & Computational biology
                long non-coding rna,immune cells,tumor immune microenvironment,bulk rna-sequencing,single-cell rna-sequencing,cell type-specific expression

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