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      Pan-cancer analysis reveals tumor-associated macrophage communication in the tumor microenvironment

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Tumor-associated macrophages (TAMs) are abundant in the tumor microenvironment (TME). However, their contribution to the immunosuppressive status of the TME remains unclear.

          Methods

          We integrated single-cell sequencing and transcriptome data from different tumor types to uncover the molecular features of TAMs. In vitro experiments and prospective clinical tests confirmed the results of these analysis.

          Results

          We first detected intra- and inter-tumoral heterogeneities between TAM subpopulations and their functions, with CD86 + TAMs playing a crucial role in tumor progression. Next, we focused on the ligand-receptor interactions between TAMs and tumor cells in different TME phenotypes and discovered that aberrant expressions of six hub genes, including FLI1, are involved in this process. A TAM-tumor cell co-culture experiment proved that FLI1 was involved in tumor cell invasion, and FLI1 also showed a unique pattern in patients. Finally, TAMs were discovered to communicate with immune and stromal cells.

          Conclusion

          We determined the role of TAMs in the TME by focusing on their communication pattern with other TME components. Additionally, the screening of hub genes revealed potential therapeutic targets.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s40164-021-00226-1.

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          Most cited references59

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          edgeR: a Bioconductor package for differential expression analysis of digital gene expression data

          Mark Robinson, Davis J. McCarthy, Gordon K. Smyth (2009)
          Summary: It is expected that emerging digital gene expression (DGE) technologies will overtake microarray technologies in the near future for many functional genomics applications. One of the fundamental data analysis tasks, especially for gene expression studies, involves determining whether there is evidence that counts for a transcript or exon are significantly different across experimental conditions. edgeR is a Bioconductor software package for examining differential expression of replicated count data. An overdispersed Poisson model is used to account for both biological and technical variability. Empirical Bayes methods are used to moderate the degree of overdispersion across transcripts, improving the reliability of inference. The methodology can be used even with the most minimal levels of replication, provided at least one phenotype or experimental condition is replicated. The software may have other applications beyond sequencing data, such as proteome peptide count data. Availability: The package is freely available under the LGPL licence from the Bioconductor web site (http://bioconductor.org). Contact: mrobinson@wehi.edu.au
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            Understanding the tumor immune microenvironment (TIME) for effective therapy

            Weiping Zou, T. Kevin Howcroft, Elisa C Woodhouse … (2018)
            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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              Macrophage activation and polarization: nomenclature and experimental guidelines.

              Peter Murray, Judith Allen, Subhra Biswas … (2014)
              Description of macrophage activation is currently contentious and confusing. Like the biblical Tower of Babel, macrophage activation encompasses a panoply of descriptors used in different ways. The lack of consensus on how to define macrophage activation in experiments in vitro and in vivo impedes progress in multiple ways, including the fact that many researchers still consider there to be only two types of activated macrophages, often termed M1 and M2. Here, we describe a set of standards encompassing three principles-the source of macrophages, definition of the activators, and a consensus collection of markers to describe macrophage activation-with the goal of unifying experimental standards for diverse experimental scenarios. Collectively, we propose a common framework for macrophage-activation nomenclature. Copyright © 2014 Elsevier Inc. All rights reserved.
              Article 0 comments Cited 1422 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Zhengxue Quan:
                ORCID: http://orcid.org/0000-0003-1778-932X
                quanzx18@126.com
                Journal
                Journal ID (nlm-ta): Exp Hematol Oncol
                Journal ID (iso-abbrev): Exp Hematol Oncol
                Title: Experimental Hematology & Oncology
                Publisher: BioMed Central (London )
                ISSN (Electronic): 2162-3619
                Publication date (Electronic): 10 May 2021
                Publication date PMC-release: 10 May 2021
                Publication date Collection: 2021
                Volume: 10
                Electronic Location Identifier: 31
                Affiliations
                [1 ]GRID grid.452206.7, Department of Orthopedic Surgery, , The First Affiliated Hospital of Chongqing Medical University, ; Chongqing, 400016 China
                [2 ]GRID grid.43169.39, ISNI 0000 0001 0599 1243, Honghui Hospital, , Xi’an Jiaotong University, ; 555 Youyi Dong Road, Beilin, Xi’an, 710054 Shaanxi China
                [3 ]Laboratory of Environmental Monitoring, Shaanxi Province Health Inspection Institution, Xi’an, 710077 Shaanxi China
                Author information
                http://orcid.org/0000-0003-1778-932X
                Article
                Publisher ID: 226
                DOI: 10.1186/s40164-021-00226-1
                PMC ID: 8108336
                PubMed ID: 33971970
                SO-VID: 39676649-7049-42fc-9087-339c37a6fdf2
                Copyright © © The Author(s) 2021
                License:

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                Date received : 24 February 2021
                Date accepted : 5 May 2021
                Categories
                Subject: Research
                Custom metadata
                issue-copyright-statement © The Author(s) 2021

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: tumor-associated macrophages,tumor microenvironment,intercellular communication,fli1
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: tumor-associated macrophages, tumor microenvironment, intercellular communication, fli1

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