# Blood Vitamin C Levels of Patients Receiving Immunotherapy and Relationship to Monocyte Subtype and Epigenetic Modification

## TL;DR

This study explores how vitamin C levels in blood relate to monocyte subtypes and epigenetic changes in patients with metastatic melanoma undergoing immunotherapy.

## Contribution

The study reveals that vitamin C levels are lower in immunotherapy patients and that correlations between ascorbate and monocyte subsets are lost in these patients.

## Key findings

- A quarter of immunotherapy patients had low vitamin C levels compared to other cancer patients and healthy controls.
- DNA methylation and ascorbate levels correlated with monocyte subsets in healthy controls but not in immunotherapy patients.
- No link was found between vitamin C status and treatment outcomes or adverse events in immunotherapy patients.

## Abstract

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.