Serum IL-10 and IL-8 Among Variable Cytokines Derived From Helper T Cells Might Be Associated with Prognoses for Malignant Lymphoma Patients
Authors: Kitagawa Junichi , Tsurumi Hisashi , Goto Naoe , Takata Katsuyoshi , Nakamura Nobuhiko , Kanemura Nobuhiro , Hara Takeshi , Kasahara Senji , Takahashi Takeshi , Yoshino Tadashi , Moriwaki Hisataka 
Published: October 2019

Abstract
Abstract 5107

Background:
Over the past few decades, investigators have worked to identify prognostic factors in non-Hodgkin lymphoma (NHL) so an appropriate therapeutic plan can be put in action. In addition to conventional prognostic factors such as the international prognostic index (IPI), many biomarkers including cytokines, chemokines, enzymes, or gene profiling have known. Recently, many researchers reported that tumor-infiltrating immune cells played an important role in host immune reaction against variable tumor cells including malignant lymphoma (ML). Variable tumor-infiltrating cells such as helper T cell, cytotoxic T cell, macrophage and mast cell were reported to give an influence for prognosis. These microenvironmental cells are influenced from variable cytokines.

Purpose:
We measured the some cytokines derived from helper T cells (Th1 and Th2) and discussed their prognostic significance for ML.

Patients and Methods:
This study was approved by our institutional review board. Consecutive 115 previously untreated patients with ML (diffuse large B-cell lymphoma (DLBCL) 56, Follicular lymphoma (FL) 19, peripheral T-cell lymphoma (PTCL-NOS) 14, mucosa associated lymphoid tissue lymphoma (MALT) 6, Hodgkin's lymphoma (HL) 5 and others 15) who were histologically diagnosed according to the WHO classification prospectively participated in this study between 2009 and 2011. We measured serum cytokines which were related with helper T cells (Th1 and Th2), such as interleukin (IL)-12p70, IFN-gamma, IL-2, IL-10, IL-6, IL-8, IL-4, IL-5, IL-1 beta, TNF alpha, and TNF beta using Flow Cytomix from eBioscience company. Patients with DLBCL received R-CHOP regimen consisted of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone with standard doses.

Result:
No significant differences were observed for serum levels between healthy control donors (HCD) and patients with ML, except for IL-10 and IL-8. The median serum level of IL-10 in ML was higher than that of HCD (ML: 0. 02 pg/ml, HCD: 0 pg/ml, p=0. 0003), and the median serum level of IL-8 was also higher in ML (ML: 49. 18 pg/ml, HCD: 0 pg/ml, p=0. 01). No significant differences were observed between B cell lymphoma and T cell lymphoma. Among DLBCL patients, higher IL-10 level group (> 0 pg/ml, detectable level) had poor prognosis than lower IL-10 level group (0 pg/ml) for overall survival (OS) and progression free survival (PFS) (3-year OS 100%, PFS 84. 0% in low IL10 group, 3-year OS 56. 3%, PFS 45. 1% in high IL10 group; OS p=0. 01; PFS p=0. 01). In addition, in low grade lymphoma including MALT, FL, mantle cell lymphoma (MCL), and small lymphocytic lymphoma (SLL), higher IL-10 level group also had poor prognoses than lower IL-10 level group in PFS (3-year PFS 83. 9%, vs. 30%, p=0. 003).

Conclusion:
IL-10 and IL-8 among variable cytokines derived from helper T cells significantly increased in the serum of untreated patients with ML and they might be associated with their prognoses. Especially, for patients with DLBCL, their cytokines might be a significant prognostic factor and a useful tool for selecting an appropriate therapeutic strategy. Further clinical investigations with a larger number of cases should be considered in future.

Disclosures:
No relevant conflicts of interest to declare.