2. Academic Validation
  3. Real-time ex vivo monitoring of NK cell migration toward obesity-associated oesophageal adenocarcinoma following modulation of CX3CR1

Real-time ex vivo monitoring of NK cell migration toward obesity-associated oesophageal adenocarcinoma following modulation of CX3CR1

  • Sci Rep. 2024 Feb 18;14(1):4017. doi: 10.1038/s41598-024-54390-5.
Eimear Mylod 1 2,  Fiona O'Connell 3,  Noel E Donlon 2,  Maria Davern 2,  Caroline Marion 1 2,  Christine Butler 3,  John V Reynolds 3,  Joanne Lysaght 2,  Melissa J Conroy 4
Affiliations

Affiliations

  • 1 Cancer Immunology Research Group, Department of Anatomy, School of Medicine, Trinity Biomedical Sciences Institute and Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland.
  • 2 Cancer Immunology and Immunotherapy Group, Department of Surgery, School of Medicine, Trinity Translational Medicine Institute and Trinity St. James's Cancer Institute, St. James's Hospital, Trinity College Dublin, Dublin, Ireland.
  • 3 Department of Surgery, School of Medicine, Trinity Translational Medicine Institute and Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland.
  • 4 Cancer Immunology Research Group, Department of Anatomy, School of Medicine, Trinity Biomedical Sciences Institute and Trinity St. James's Cancer Institute, Trinity College Dublin, Dublin, Ireland. meconroy@tcd.ie.
PMID: 38369570 DOI: 10.1038/s41598-024-54390-5
Abstract

Oesophagogastric adenocarcinomas (OAC) are poor prognosis, obesity-associated cancers which may benefit from natural killer (NK) cell-based immunotherapies. Cellular immunotherapies encounter two key challenges to their success in OAC, namely recruitment to extratumoural tissues such as the omentum at the expense of the tumour and an immunosuppressive tumour microenvironment (TME) which can hamper NK cell function. Herein, we examined approaches to overcome the detrimental impact of obesity on NK cells and NK cell-based immunotherapies. We have demonstrated that NK cells migrate preferentially to the chemotactic signals of OAC patient-derived omentum over tumour in an ex vivo model of immune cell migration. We have identified CX3CR1 modulation and/or tumour chemokine profile remodelling as approaches to skew NK cell migration towards tumour. We also report targetable immunosuppressive facets of the obese OAC TME which dampen NK cell function, in particular cytotoxic capabilities. These data provide insights into approaches to therapeutically overcome key challenges presented by obesity and will inform superior design of NK cell-based immunotherapies for OAC.

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