Vitreous levels of interleukin-35 as a prognostic factor in B-cell vitreoretinal lymphoma

Atsunobu Takeda,Hiroshi Yoshikawa,Koh-Hei Sonoda,Keijiro Ishikawa,Yusuke Murakami,Nobuyo Yawata,Eiichi Hasegawa,Yoshinao Oda,Mitsuru Arima,Shintaro Nakao,Toshio Hisatomi,Kazuhiro Kimura

doi:10.1038/s41598-020-72962-z

Atsunobu Takeda, Hiroshi Yoshikawa + Show 10 more

Open Access

https://doi.org/10.1038/s41598-020-72962-z

Copy DOI

Abstract

Vitreoretinal lymphoma (VRL) is a rare disease of B-cell origin with poor prognosis. Regulatory cytokines promote tumor development by suppressing antitumor immunity in several cancer types, including B-cell malignancies. To identify the regulatory cytokines associated with poor prognosis in patients with B-cell VRL, we determined the regulatory cytokines profiles in the vitreous humor of patients with VRL. This retrospective study included 22 patients with VRL, 24 with non-infectious uveitis (NIU), and 20 with idiopathic epiretinal membrane (control). Vitreous concentrations of regulatory cytokines were assessed using a cytometric beads assay and association with clinical data was examined. IL-35 and soluble IL-2 receptor α levels were significantly higher in patients with VRL and NIU than those in the control group. The 5-year overall survival (OS) rates for the group with high intravitreal IL-35 was significantly poorer than those for the group with low intravitreal IL-35, who were diagnosed with VRL at the onset (P = 0.024, log-rank test). The 5-year OS rates with intravitreal IL-35 levels above and below the median were 40.0% and 83.3%, respectively. Our results suggest that high intravitreal IL-35 levels indicate poor prognosis for patients diagnosed with B-cell VRL at the onset.

Highlights

Vitreoretinal lymphoma (VRL) is a rare disease of B-cell origin with poor prognosis
IL-10, IL-20, IL-22, IL-27, IL-35, and soluble IL-2 receptor α levels were significantly different among patients with controls, VRL, and non-infectious uveitis (NIU) (Table 2; P < 0.001, P < 0.001, P = 0.0011, P = 0.026, P < 0.001, P < 0.001, respectively)
programmed cell death-1 (PD-1), which is expressed on activated T-cells, such as cytotoxic T lymphocytes (CTLs), interacts with its ligands PD-L1 and PD-L2, which are commonly expressed by tumor cells, leading to enhanced inhibitory signaling of T-cell receptor in C TLs29,30

Summary

Introduction

Vitreoretinal lymphoma (VRL) is a rare disease of B-cell origin with poor prognosis. Regulatory cytokines promote tumor development by suppressing antitumor immunity in several cancer types, including B-cell malignancies. To identify the regulatory cytokines associated with poor prognosis in patients with B-cell VRL, we determined the regulatory cytokines profiles in the vitreous humor of patients with VRL. This retrospective study included 22 patients with VRL, 24 with non-infectious uveitis (NIU), and 20 with idiopathic epiretinal membrane (control). Our results suggest that high intravitreal IL-35 levels indicate poor prognosis for patients diagnosed with B-cell VRL at the onset. We assessed the association of regulatory cytokines with clinical parameters in B-cell VRL patients; and observed that higher levels of IL-35 in the vitreous humor were positively correlated with a poor prognosis in B-cell VRL patients with vitreoretinal lesions at initial diagnosis

Objectives

Methods

Results

Conclusion