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      Allogenic Vγ9Vδ2 T cell as new potential immunotherapy drug for solid tumor: a case study for cholangiocarcinoma

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          Abstract

          Background

          Cholangiocarcinoma (CCA) is a highly aggressive and fatal tumor. CCA occurs in the epithelial cells of bile ducts. Due to increasing incidences, CCA accounts for 3% of all gastrointestinal malignancies. In addition to comprehensive treatments for cancer, such as surgery, chemotherapy, and radiotherapy, during the past few years, cellular immunotherapy has played an increasingly important role. As a result of our research, we have discovered the γδ T cell-based immunotherapy for CCA.

          Case presentation

          A 30-year-old male ( https://www.clinicaltrials.gov/ ID: NCT02425735) was diagnosed with recurrent mediastinal lymph node metastasis after liver transplantation because of Cholangiocarcinoma (stage IV). In the course of his therapy sessions, he only received allogenic γδ T cell immunotherapy from August, 2017 through February, 2018 (8 infusions in total). γδ T cells were expanded from peripheral blood mononuclear cells (PBMCs) of healthy donor, and ~ 4 × 10 8 cells were adoptive transferred to the patient.

          Conclusion

          In the above case report of the Cholangiocarcinoma (stage IV) patient who had received liver transplantation and afterward was diagnosed with recurrent mediastinal lymph node metastasis, we clinically proved that allogenic γδ T cell treatment had no adverse effects. We observed that allogenic γδ T cell treatments positively regulated peripheral immune functions of the patient, depleted tumor activity, improved quality of life, and prolonged his life span. After 8 γδ T cell treatments, the size of lymph nodes was remarkably reduced with activity depletion. This clinical work suggested that allogenic γδ T cell immunotherapy could be developed into a promising therapy drug for CCA.

          Electronic supplementary material

          The online version of this article (10.1186/s40425-019-0501-8) contains supplementary material, which is available to authorized users.

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          Most cited references 31

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          The epidemiology of cholangiocarcinoma.

          The incidence rates of cholangiocarcinoma (CC) vary greatly among different areas of the world, and this variation is related to distribution of risk factors. Intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) have different epidemiological features. Recent data show that the incidence and mortality rates of ICC have been increasing in several areas around the world. On the other hand, the incidence and mortality rates of ECC have been decreasing. For example, in the United States, the age-adjusted incidence rates of ICC increased by 165% from 0.32 per 100,000 in 1975 to 1979 to 0.85 per 100,000 in 1995 to 1999, whereas ECC declined by 14%. In the meantime, there has been very little improvement in long-term survival, which remains dismal (3.5%). Men are affected 1.5 times more than women are, and Asians are affected almost 2 times more than whites and blacks. There are few well-established risk factors for CC, including primary sclerosing cholangitis, liver fluke infestations, hepatolithiasis, Thorotrast exposure, and choledochal cysts. None of these risk factors can explain the recent increasing trends of ICC in the United States. Some data, however, point to a potential role for chronic liver disease, hepatitis C, and probably hepatitis B infections in the development of ICC.
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            Gammadelta T cell effector functions: a blend of innate programming and acquired plasticity.

            Gammadelta T cells have several innate cell-like features that allow their early activation following recognition of conserved stress-induced ligands. Here we review recent observations revealing the ability of gammadelta T cells to rapidly produce cytokines that regulate pathogen clearance, inflammation and tissue homeostasis in response to tissue stress. These studies provide insights into how they acquire these properties, through both developmental programming in the thymus and functional polarization in the periphery. Innate features of gammadelta T cells underlie their non-redundant role in several physiopathological contexts and are therefore being exploited in the design of new immunotherapeutic approaches.
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              Guidelines for the diagnosis and management of intrahepatic cholangiocarcinoma.

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                Author and article information

                Affiliations
                [1 ]ISNI 0000 0004 1790 3548, GRID grid.258164.c, Biomedical Translational Research Institute and The First Affiliated Hospital, , Jinan University, ; 601 W Ave Huangpu, Guangzhou, 510632 Guangdong People’s Republic of China
                [2 ]ISNI 0000 0004 1790 3548, GRID grid.258164.c, Department of Oncology, Fuda Cancer Hospital, School of Medicine, , Jinan University, ; Guangzhou, 510665 Guangdong People’s Republic of China
                [3 ]ISNI 0000 0004 1790 3548, GRID grid.258164.c, Department of Biological Treatment Center, Fuda Cancer Hospital, School of Medicine, , Jinan University, ; Guangzhou, 510665 Guangdong People’s Republic of China
                Contributors
                xukc@vip.163.com
                tyzwu@jnu.edu.cn
                zhinan.yin@yale.edu
                Journal
                J Immunother Cancer
                J Immunother Cancer
                Journal for Immunotherapy of Cancer
                BioMed Central (London )
                2051-1426
                8 February 2019
                8 February 2019
                2019
                : 7
                501
                10.1186/s40425-019-0501-8
                6368763
                30736852
                © The Author(s). 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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.

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                © The Author(s) 2019

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