title: Dexamethasone co-medication in cancer patients undergoing chemotherapy causes substantial immunomodulatory effects with implications for chemo-immunotherapy strategies.
abstract: The glucocorticoid (GC) steroid dexamethasone (Dex) is used as a supportive care co-medication for cancer patients undergoing standard care pemetrexed/platinum doublet chemotherapy. As trials for new cancer immunotherapy treatments increase in prevalence, it is important to track the immunological changes induced by co-medications commonly used in the clinic, but not specifically included in trial design or in pre-clinical models. Here, we document a number of Dex -induced immunological effects, including a large-scale lymphodepletive effect particularly affecting CD4+T cells but also CD8+T cells. The proportion of regulatory T cells within the CD4+compartment did not change after Dex was administered, however a significant increase in proliferation and activation of regulatory T cells was observed. We also noted Dex -induced proportional changes in dendritic cell (DC) subtypes. We discuss these immunological effects in the context of chemoimmunotherapy strategies, and suggest a number of considerations to be taken into account when designing future studies where Dex and other GCs may be in use.
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia; National Centre for Asbestos Related Diseases, Perth, WA, Australia.
authors.forename: Alistair M
authors.initials: AM
authors.lastname: Cook
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia; National Centre for Asbestos Related Diseases, Perth, WA, Australia.
authors.forename: Alison M
authors.initials: AM
authors.lastname: McDonnell
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia; National Centre for Asbestos Related Diseases, Perth, WA, Australia.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lake
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia; Department of Medical Oncology, Sir Charles Gairdner Hospital, Perth, WA, Australia; National Centre for Asbestos Related Diseases, Perth, WA, Australia.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Nowak
keywords: Immunotherapy; T cell; dendritic cell; flow cytometry; glucocorticoid; lymphodepletion; mesothelioma; treg