Presence and Characterization of Th17 Cells in the Tumoral Microenvironment of Primary Intraocular B-Cell Lymphoma

Abstract

Purpose: : Despite the important role of Th17 cells in the pathogenesis of many autoimmune diseases, their presence and role in cancer remain unclear. In this work, we investigated the presence of Th17 cells and their related cytokines in a syngeneic model of primary intraocular B-cell lymphoma (PIOL) which is a subtype of non Hodgkin lymphomas. Since there is no resident lymphocyte in a normal eye, this model allows to characterize the different lymphocyte subsets attracted by the tumor.

Methods: : The murine lymphomatous B-cell line A20-IIA1.6 (H2^d) was injected in the posterior chamber of immunocompetent adult BALB/c mice (H2^d) and flow cytometric analysis were performed to study tumor growth and immune infiltrate. Cytokine production of ocular cells was investigated by RT-PCR and fluorescent immunoassay with or without stimulation by anti-CD3 plus anti-CD28 antibodies.

Results: : Concomitantly to the presence of prepolarized Th1 lymphocytes and CD4⁺Foxp3⁺ cells, Th17 cells were found and characterized by the intracellular expression of IL-17 and IL-21, but no IFNγ. At the molecular level, RT-PCR analysis demonstrated the ocular expression of IL-17, IL-21 and IL-23 mRNAs. Interestingly, IL-17 protein level measured by cytometric bead array showed an inverted correlation with the tumor burden.

Conclusions: : These data demonstrate that a local infiltration of IL-17 and IL-21 secreting cells occurs in a tumoral context, and suggests that Th17-related cytokines counteract the tumor development. Thus, use of Th17 cells or their related cytokines should be considered as a new therapeutic approach for non Hodgkin B-cell lymphomas and particularly with an ocular localization.

Keywords: tumors • cytokines/chemokines • flow cytometry