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      Leukocyte immunoglobulin-like receptor subfamily B: therapeutic targets in cancer

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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

          Inhibitory leukocyte immunoglobulin-like receptors (LILRBs 1–5) transduce signals via intracellular immunoreceptor tyrosine-based inhibitory motifs that recruit phosphatases to negatively regulate immune activation. The activation of LILRB signaling in immune cells may contribute to immune evasion. In addition, the expression and signaling of LILRBs in cancer cells especially in certain hematologic malignant cells directly support cancer development. Certain LILRBs thus have dual roles in cancer biology—as immune checkpoint molecules and tumor-supporting factors. Here, we review the expression, ligands, signaling, and functions of LILRBs, as well as therapeutic development targeting them. LILRBs may represent attractive targets for cancer treatment, and antagonizing LILRB signaling may prove to be effective anti-cancer strategies.

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          Most cited references295

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          Tumour-associated macrophages as treatment targets in oncology

          Alberto Mantovani, Federica Marchesi, Alberto Malesci … (2017)
          Tumour-associated macrophages (TAMs) are key drivers of tumour-promoting inflammation and cancer progression, and are important determinants of responsiveness to a range of therapies. Herein, the authors summarize the roles of TAMs in cancer, and discuss the potential of TAM-targeted therapeutic strategies to complement and synergize with other anticancer treatments.
          Article 0 comments Cited 1179 times – based on 0 reviews     Review now
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            Fundamental Mechanisms of Immune Checkpoint Blockade Therapy

            Spencer Wei, James P Allison, Colm Duffy (2018)
            Immune checkpoint blockade is able to induce durable responses across multiple types of cancer, which has enabled the oncology community to begin to envision potentially curative therapeutic approaches. However, the remarkable responses to immunotherapies are currently limited to a minority of patients and indications, highlighting the need for more effective and novel approaches. Indeed, an extraordinary amount of preclinical and clinical investigation is exploring the therapeutic potential of negative and positive costimulatory molecules. Insights into the underlying biological mechanisms and functions of these molecules have, however, lagged significantly behind. Such understanding will be essential for the rational design of next-generation immunotherapies. Here, we review the current state of our understanding of T-cell costimulatory mechanisms and checkpoint blockade, primarily of CTLA4 and PD-1, and highlight conceptual gaps in knowledge.Significance: This review provides an overview of immune checkpoint blockade therapy from a basic biology and immunologic perspective for the cancer research community. Cancer Discov; 8(9); 1069-86. ©2018 AACR.
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              Tumor-associated macrophages: from mechanisms to therapy.

              Roy Noy, Jeffrey W Pollard (2014)
              The tumor microenvironment is a complex ecology of cells that evolves with and provides support to tumor cells during the transition to malignancy. Among the innate and adaptive immune cells recruited to the tumor site, macrophages are particularly abundant and are present at all stages of tumor progression. Clinical studies and experimental mouse models indicate that these macrophages generally play a protumoral role. In the primary tumor, macrophages can stimulate angiogenesis and enhance tumor cell invasion, motility, and intravasation. During monocytes and/or metastasis, macrophages prime the premetastatic site and promote tumor cell extravasation, survival, and persistent growth. Macrophages are also immunosuppressive, preventing tumor cell attack by natural killer and T cells during tumor progression and after recovery from chemo- or immunotherapy. Therapeutic success in targeting these protumoral roles in preclinical models and in early clinical trials suggests that macrophages are attractive targets as part of combination therapy in cancer treatment. Copyright © 2014 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Mi Deng:
                ORCID: https://orcid.org/0000-0003-4291-0144
                Heyu Chen
                Xiaoye Liu
                Ryan Huang
                Yubo He
                Byounggyu Yoo
                Jingjing Xie
                Samuel John
                Ningyan Zhang
                Zhiqiang An:
                ORCID: https://orcid.org/0000-0001-9309-2335
                Cheng Cheng Zhang
                Journal
                Journal ID (nlm-ta): Antib Ther
                Journal ID (iso-abbrev): Antib Ther
                Journal ID (publisher-id): anther
                Title: Antibody Therapeutics
                Publisher: Oxford University Press
                ISSN (Electronic): 2516-4236
                Publication date Collection: January 2021
                Publication date (Electronic): 09 February 2021
                Publication date PMC-release: 09 February 2021
                Volume: 4
                Issue: 1
                Pages: 16-33
                Affiliations
                Department of Physiology , University of Texas Southwestern Medical Center , Dallas, TX 75390, USA
                Department of Physiology , University of Texas Southwestern Medical Center , Dallas, TX 75390, USA
                Department of Physiology , University of Texas Southwestern Medical Center , Dallas, TX 75390, USA
                Department of Physiology , University of Texas Southwestern Medical Center , Dallas, TX 75390, USA
                Department of Physiology , University of Texas Southwestern Medical Center , Dallas, TX 75390, USA
                Department of Physiology , University of Texas Southwestern Medical Center , Dallas, TX 75390, USA
                Department of Physiology , University of Texas Southwestern Medical Center , Dallas, TX 75390, USA
                Department of Pediatrics , Pediatric Hematology-Oncology, University of Texas Southwestern Medical Center , Dallas, TX 75390, USA
                Texas Therapeutics Institute , Brown Foundation Institute of Molecular Medicine, University of Texas Houston Health Science Center , Houston, TX 77030, USA
                Texas Therapeutics Institute , Brown Foundation Institute of Molecular Medicine, University of Texas Houston Health Science Center , Houston, TX 77030, USA
                Department of Physiology , University of Texas Southwestern Medical Center , Dallas, TX 75390, USA
                Author notes
                To whom correspondence should be addressed. Cheng Cheng Zhang. Tel.: +1-214-645-6320; Fax: +1-214-648-1960; Email: Alec.Zhang@ 123456UTSouthwestern.edu
                Author information
                https://orcid.org/0000-0003-4291-0144
                https://orcid.org/0000-0001-9309-2335
                Article
                Publisher ID: tbab002
                DOI: 10.1093/abt/tbab002
                PMC ID: 7944505
                PubMed ID: 33928233
                SO-VID: 138e231c-ed1f-44a1-80cf-8249de00e2c5
                Copyright © © The Author(s) 2021. Published by Oxford University Press on behalf of Antibody Therapeutics. All rights reserved. For Permissions, please email: journals.permissions@oup.com
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://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
                Date received : 30 October 2020
                Date revision received : 12 January 2021
                Date accepted : 13 January 2021
                Page count
                Pages: 18
                Funding
                Funded by: National Cancer Institute, DOI 10.13039/100000054;
                Award ID: 1R01 CA248736
                Funded by: Cancer Prevention and Research Institute of Texas, DOI 10.13039/100004917;
                Award ID: RP180435
                Award ID: RP150551
                Award ID: RP190561
                Funded by: Immune-Onc Therapeutics;
                Award ID: #111077
                Categories
                Subject: Review Article
                Subject: AcademicSubjects/SCI01030
                Subject: AcademicSubjects/SCI00100

                Keywords: immunoreceptor tyrosine-based inhibitory motif,itim,immunoglobulin-like domain,immune inhibitory receptor,leukocyte immunoglobulin-like receptor subfamily b,lilrb,signal transduction,cancer
                Data availability:
                Keywords: immunoreceptor tyrosine-based inhibitory motif, itim, immunoglobulin-like domain, immune inhibitory receptor, leukocyte immunoglobulin-like receptor subfamily b, lilrb, signal transduction, cancer

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