title: Standard radiotherapy but not chemotherapy impairs systemic immunity in non-small cell lung cancer.
abstract: Introduction: Advanced non-small cell lung cancer (NSCLC) is traditionally treated with platinum-based chemotherapy and radiotherapy. Since immunotherapy holds promise for treating advanced NSCLC, we assessed the systemic effects of the traditional therapies for NSCLC on immune cell composition and function.Methods: 84 pulmonary adenocarcinoma patients, treated either with chemotherapy or radiotherapy, were studied. A prospective study of 23 patients was conducted in which the myeloid and lymphoid cell compartments of peripheral blood were analyzed. Changes in cell populations were validated in a retrospective cohort of 61 adenocarcinoma patients using automated differential counts collected throughout therapy. Furthermore, the functional capacity of circulating T cells and antigen-presenting cells (APC) was studied. Blood samples of healthy individuals were used as controls.Results: In comparison to healthy controls, untreated adenocarcinoma patients display an elevated frequency of myeloid cells coinciding with relative lower frequencies of lymphocytes and dendritic cells. Standard chemotherapy had no overt effects on myeloid and lymphoid cell composition nor on T-cell and APC-function. In contrast, patients treated with radiotherapy displayed a decrease in lymphoid cells and a relative increase in monocytes/macrophages. Importantly, these changes were associated with a reduced APC function and an impaired response of T cells to recall antigens.Conclusions: Platinum-based standard of care chemotherapy for NSCLC has no profound negative effect on the immune cell composition and function. The negative effect of prolonged low-dose radiotherapy on the immune system warrants future studies on the optimal dose and fraction of radiotherapy when combined with immunotherapy.
authors.affiliation: Department of Pulmonology, Leiden University Medical Center , Leiden, the Netherlands.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Talebian Yazdi
authors.affiliation: Department of Pulmonology, Leiden University Medical Center , Leiden, the Netherlands.
authors.forename: Mink S
authors.initials: MS
authors.lastname: Schinkelshoek
authors.affiliation: Department of Medical Oncology, Leiden University Medical Center , Leiden, the Netherlands.
authors.forename: Nikki M
authors.initials: NM
authors.lastname: Loof
authors.affiliation: Department of Pulmonology, Leiden University Medical Center , Leiden, the Netherlands.
authors.forename: Christian
authors.initials: C
authors.lastname: Taube
authors.affiliation: Department of Pulmonology, Leiden University Medical Center , Leiden, the Netherlands.
authors.forename: Pieter S
authors.initials: PS
authors.lastname: Hiemstra
authors.affiliation: Department of Medical Oncology, Leiden University Medical Center , Leiden, the Netherlands.
authors.forename: Marij J P
authors.initials: MJ
authors.lastname: Welters
authors.affiliation: Department of Medical Oncology, Leiden University Medical Center , Leiden, the Netherlands.
authors.forename: Sjoerd H
authors.initials: SH
authors.lastname: van der Burg
keywords: Chemotherapy; T cells; immunity; immunotherapy; myeloid cells; radiotherapy