In vitro humanized 3D microfluidic chip for testing personalized immunotherapeutics for head and neck cancer patients

Ahmed Al-Samadi; Benedek Poor; Katja Tuomainen; Ville Liu; Aini Hyytiäinen; Ilida Suleymanova; Karri Mesimaki; Tommy Wilkman; Antti Mäkitie; Päivi Saavalainen; Tuula Salo

doi:10.1016/j.yexcr.2019.111508

In vitro humanized 3D microfluidic chip for testing personalized immunotherapeutics for head and neck cancer patients

Exp Cell Res. 2019 Oct 15;383(2):111508. doi: 10.1016/j.yexcr.2019.111508. Epub 2019 Jul 26.

Authors

Affiliations

¹ Department 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.
² Translational 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.
³ Department 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.
⁴ Department of Oral and Maxillofacial Surgery, HUS Helsinki University Hospital, Finland.
⁵ Department 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.
⁶ Department 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Antineoplastic Agents, Immunological / isolation & purification
Antineoplastic Agents, Immunological / therapeutic use*
Biomarkers, Pharmacological / analysis
Cell Migration Assays / instrumentation
Cell Migration Assays / methods
Cell Movement / drug effects
Coculture Techniques / instrumentation
Coculture Techniques / methods
Drug Screening Assays, Antitumor / instrumentation
Drug Screening Assays, Antitumor / methods
Equipment Design
Female
Head and Neck Neoplasms / diagnosis
Head and Neck Neoplasms / pathology*
Head and Neck Neoplasms / therapy
Humans
Immunologic Factors / isolation & purification
Immunologic Factors / therapeutic use
Immunotherapy* / instrumentation
Immunotherapy* / methods
Lab-On-A-Chip Devices*
Male
Microfluidics / instrumentation
Microfluidics / methods
Middle Aged
Precancerous Conditions / diagnosis
Precancerous Conditions / drug therapy
Precancerous Conditions / pathology
Precision Medicine* / instrumentation
Precision Medicine* / methods
Primary Cell Culture / instrumentation
Primary Cell Culture / methods*
Prognosis
Squamous Cell Carcinoma of Head and Neck / diagnosis
Squamous Cell Carcinoma of Head and Neck / pathology*
Squamous Cell Carcinoma of Head and Neck / therapy
Tissue Scaffolds
Tumor Cells, Cultured

Substances

Antineoplastic Agents, Immunological
Biomarkers, Pharmacological
Immunologic Factors