Blood Vitamin C Levels of Patients Receiving Immunotherapy and Relationship to Monocyte Subtype and Epigenetic Modification
Ben Topham,
Millie de Vries,
Maria Nonis,
Rebecca van Berkel,
Juliet M. Pullar,
Nicholas J. Magon,
Margreet C. M. Vissers,
Margaret J. Currie,
Bridget A. Robinson,
David Gibbs,
Abel Ang,
Gabi U. Dachs
Affiliations
Ben Topham
Mackenzie Cancer Research Group, Department of Pathology and Biomedical Science, University of Otago Christchurch, Christchurch 8011, New Zealand
Millie de Vries
Mackenzie Cancer Research Group, Department of Pathology and Biomedical Science, University of Otago Christchurch, Christchurch 8011, New Zealand
Maria Nonis
Mackenzie Cancer Research Group, Department of Pathology and Biomedical Science, University of Otago Christchurch, Christchurch 8011, New Zealand
Rebecca van Berkel
Mackenzie Cancer Research Group, Department of Pathology and Biomedical Science, University of Otago Christchurch, Christchurch 8011, New Zealand
Juliet M. Pullar
Mātai Hāora—Centre for Redox Biology and Medicine, Department of Pathology and Biomedical Science, University of Otago Christchurch, Christchurch 8011, New Zealand
Nicholas J. Magon
Mātai Hāora—Centre for Redox Biology and Medicine, Department of Pathology and Biomedical Science, University of Otago Christchurch, Christchurch 8011, New Zealand
Margreet C. M. Vissers
Mātai Hāora—Centre for Redox Biology and Medicine, Department of Pathology and Biomedical Science, University of Otago Christchurch, Christchurch 8011, New Zealand
Margaret J. Currie
Mackenzie Cancer Research Group, Department of Pathology and Biomedical Science, University of Otago Christchurch, Christchurch 8011, New Zealand
Bridget A. Robinson
Mackenzie Cancer Research Group, Department of Pathology and Biomedical Science, University of Otago Christchurch, Christchurch 8011, New Zealand
David Gibbs
Canterbury Regional Cancer and Haematology Service, Te Whatu Ora Waitaha, Canterbury, Christchurch 8011, New Zealand
Abel Ang
Mackenzie Cancer Research Group, Department of Pathology and Biomedical Science, University of Otago Christchurch, Christchurch 8011, New Zealand
Gabi U. Dachs
Mackenzie Cancer Research Group, Department of Pathology and Biomedical Science, University of Otago Christchurch, Christchurch 8011, New Zealand
The treatment of metastatic melanoma has been revolutionised by immunotherapy, yet a significant number of patients do not respond, and many experience autoimmune adverse events. Associations have been reported between patient outcome and monocyte subsets, whereas vitamin C (ascorbate) has been shown to mediate changes in cancer-stimulated monocytes in vitro. We therefore investigated the relationship of ascorbate with monocyte subsets and epigenetic modifications in patients with metastatic melanoma receiving immunotherapy. Patients receiving immunotherapy were compared to other cancer cohorts and age-matched healthy controls. Ascorbate levels in plasma and peripheral blood-derived mononuclear cells (PBMCs), monocyte subtype and epigenetic markers were measured, and adverse events, tumour response and survival were recorded. A quarter of the immunotherapy cohort had hypovitaminosis C, with plasma and PBMC ascorbate levels significantly lower than those from other cancer patients or healthy controls. PBMCs from the immunotherapy cohort contained similar frequencies of non-classical and classical monocytes. DNA methylation markers and intracellular ascorbate concentration were correlated with monocyte subset frequency in healthy controls, but correlation was lost in immunotherapy patients. No associations between ascorbate status and immune-related adverse events or tumour response or overall survival were apparent.
