. 2019 Oct 15;383(2):111508.

 doi: 10.1016/j.yexcr.2019.111508. Epub 2019 Jul 26.

In Vitro Humanized 3D Microfluidic Chip for Testing Personalized Immunotherapeutics for Head and Neck Cancer Patients

Ahmed Al-Samadi 1, Benedek Poor 2, Katja Tuomainen 3, Ville Liu 3, Aini Hyytiäinen 3, Ilida Suleymanova 3, Karri Mesimaki 4, Tommy Wilkman 4, Antti Mäkitie 5, Päivi Saavalainen 2, Tuula Salo 6

Affiliations 

Affiliations

• 1Department of Oral and Maxillofacial Diseases, Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland. Electronic address: ahmed.al-samadi@helsinki.fi.
• 2Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Department of Medical and Clinical Genetics, Medicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
• 3Department of Oral and Maxillofacial Diseases, Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
• 4Department of Oral and Maxillofacial Surgery, HUS Helsinki University Hospital, Finland.
• 5Department of Otorhinolaryngology - Head and Neck Surgery, HUS Helsinki University Hospital and University of Helsinki, Helsinki, Finland; Division of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Research Program in Systems Oncology, Faculty of Medicine, University of Helsinki, Finland.
• 6Department of Oral and Maxillofacial Diseases, Clinicum, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Translational Immunology Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland; Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland; Medical Research Centre, Oulu University Hospital, Oulu, Finland; Helsinki University Hospital, Helsinki, Finland.

• PMID: 31356815
 
• DOI: 10.1016/j.yexcr.2019.111508

Abstract

Objectives: Immunotherapy and personalized medicine therapeutics are emerging as promising approaches in the management of head and neck squamous cell carcinoma (HNSCC). In spite of that, there is yet no assay that could predict individual response to immunotherapy.

Methods: We manufactured an in vitro 3D microfluidic chip to test the efficacy of immunotherapy. The assay was first tested using a tongue cancer cell line (HSC-3) embedded in a human tumour-derived matrix "Myogel/fibrin" and immune cells from three healthy donors. Next, the chips were used with freshly isolated cancer cells, patients' serum and immune cells. Chips were loaded with different immune checkpoint inhibitors, PD-L1 antibody and IDO 1 inhibitor. Migration of immune cells towards cancer cells and the cancer cell proliferation rate were evaluated.

Results: Immune cell migration towards HSC-3 cells was cancer cell density dependent. IDO 1 inhibitor induced immune cells to migrate towards cancer cells both in HSC-3 and in two HNSCC patient samples. Efficacy of PD-L1 antibody and IDO 1 inhibitor was patient dependent.

Conclusion: We introduced the first humanized in vitro microfluidic chip assay to test immunotherapeutic drugs against HNSCC patient samples. This assay could be used to predict the efficacy of immunotherapeutic drugs for individual patients.

Keywords: Head and neck cancer; IDO1; Immunotherapy; In vitro; Microfuidic chip; PD-L1; Personalized medicine.

Copyright © 2019 Elsevier Inc. All rights reserved.

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. 2020 Jun 26;S1879-7296(20)30147-2.

 doi: 10.1016/j.anorl.2020.06.008. Online ahead of print.

Pasteurella Multocida Acute Epiglottitis

L Jan 1, P Boute 2, F Mouawad 3

Affiliations 

Affiliations

• 1Service d'ORL et CCF, Hôpital Huriez, CHU de Lille, 1 place de Verdun, 59037 Lille cedex, France.
• 2Service d'ORL et CCF, Centre Hospitalier de Boulogne sur Mer, 62321 Boulogne sur Mer, France.
• 3Service d'ORL et CCF, Hôpital Huriez, CHU de Lille, 1 place de Verdun, 59037 Lille cedex, France; INSERM U 908, Université des Sciences et Technologies de Lille, UFR de Biologie - SN3, 59655 Villeneuve d'Ascq, France. Electronic address: francois.mouawad@chru-lille.fr.

• PMID: 32600824
 
• DOI: 10.1016/j.anorl.2020.06.008

Abstract

Introduction: Apart from cases related to direct inoculation, pasteurellosis is a rare opportunistic infection occurring in predisposed subjects. Close contact with domestic animals, usually cats, is generally reported. Localized ENT forms are possible and are due to oropharyngeal carriage.

Case report: We present the case of a patient with no notable history, who presented with laryngeal dyspnea and hyperthermia leading to a diagnosis of acute epiglottitis. Bacteremia was detected and blood cultures were positive for Pasteurella multocida. Treatment consisted of the standard treatment for acute epiglottitis with hospitalisation and intravenous antibiotics.

Discussion: This patient presented a history of animal exposure, but no other known risk factors. The activity spectrum of antibiotic therapy for epiglottitis should include H. influenzae and this case illustrates the diversity of the micro-organisms potentially involved. Immunosuppression or another chronic disease does not appear to be a prerequisite for ENT infection.

Keywords: Epiglottitis; Pasteurella multocida; Septicemia; Zoonosis.

Copyright © 2020 Elsevier Masson SAS. All rights reserved.