4
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Humanized Mice as a Valuable Pre-Clinical Model for Cancer Immunotherapy Research

      review-article

      Read this article at

      Bookmark
          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

          Immunotherapy with checkpoint inhibitors opened new horizons in cancer treatment. Clinical trials for novel immunotherapies or unexplored combination regimens either need years of development or are simply impossible to perform like is the case in cancer patients with limited life expectancy. Thus, the need for preclinical models that rapidly and safely allow for a better understanding of underlying mechanisms, drug kinetics and toxicity leading to the selection of the best regimen to be translated into the clinic, is of high importance. Humanized mice that can bear both human immune system and human tumors, are increasingly used in recent preclinical immunotherapy studies and represent a remarkably unprecedented tool in this field. In this review, we describe, summarize, and discuss the recent advances of humanized mouse models used for cancer immunotherapy research and the challenges faced during their establishment. We also highlight the lack of preclinical studies using this model for radiotherapy-based research and argue that it can be a great asset to understand and answer many open questions around radiation therapy such as its presumed associated “abscopal effect”.

          Related collections

          Most cited references98

          • Record: found
          • Abstract: found
          • Article: found

          Hallmarks of Cancer: The Next Generation

          The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer. Copyright © 2011 Elsevier Inc. All rights reserved.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Of Mice and Not Men: Differences between Mouse and Human Immunology

              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity

              Radiotherapy is under investigation for its ability to enhance responses to immunotherapy. However, the mechanisms by which radiation induces anti-tumour T cells remain unclear. We show that the DNA exonuclease Trex1 is induced by radiation doses above 12–18 Gy in different cancer cells, and attenuates their immunogenicity by degrading DNA that accumulates in the cytosol upon radiation. Cytosolic DNA stimulates secretion of interferon-β by cancer cells following activation of the DNA sensor cGAS and its downstream effector STING. Repeated irradiation at doses that do not induce Trex1 amplifies interferon-β production, resulting in recruitment and activation of Batf3-dependent dendritic cells. This effect is essential for priming of CD8+ T cells that mediate systemic tumour rejection (abscopal effect) in the context of immune checkpoint blockade. Thus, Trex1 is an upstream regulator of radiation-driven anti-tumour immunity. Trex1 induction may guide the selection of radiation dose and fractionation in patients treated with immunotherapy.
                Bookmark

                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                18 November 2021
                2021
                : 11
                : 784947
                Affiliations
                [1] 1 Department of Radiation Oncology, Institut Jules Bordet, Université Libre de Bruxelles , Brussels, Belgium
                [2] 2 Laboratory of Clinical and Experimental Oncology (LOCE), Institut Jules Bordet, Université Libre de Bruxelles , Brussels, Belgium
                [3] 3 Laboratory of Cellular Therapy (UTCH), Institut Jules Bordet, Université Libre de Bruxelles , Brussels, Belgium
                [4] 4 Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles , Brussels, Belgium
                Author notes

                Edited by: Sandra Tuyaerts, University Hospital Brussels, Belgium

                Reviewed by: Todd M. Pitts, University of Colorado, United States; Daniela Annibali, KU Leuven, Belgium

                *Correspondence: Mohammad Krayem, Mohammad.krayem@ 123456bordet.be

                This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Oncology

                Article
                10.3389/fonc.2021.784947
                8636317
                34869042
                9cc9b6f8-ecb8-412d-b44a-1b3bf8795546
                Copyright © 2021 Cogels, Rouas, Ghanem, Martinive, Awada, Van Gestel and Krayem

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 28 September 2021
                : 29 October 2021
                Page count
                Figures: 2, Tables: 3, Equations: 0, References: 98, Pages: 13, Words: 5901
                Categories
                Oncology
                Review

                Oncology & Radiotherapy
                humanized mice,preclinical model,cancer,immunotherapy,oncoimmunology
                Oncology & Radiotherapy
                humanized mice, preclinical model, cancer, immunotherapy, oncoimmunology

                Comments

                Comment on this article