Abstract
BackgroundTh17 cells play an important role in the pathogenesis of many autoimmune diseases, but despite some reports of their antitumor properties, too little is known about their presence and role in cancers. Specifically, knowledge is sparse about the relation of Th17 to lymphoma microenvironments and, more particularly, to the microenvironment of primary intraocular B-cell lymphoma (PIOL), an aggressive lymphoma with a poor prognosis.Methods and Principal FindingsIn this work, we investigated the presence of Th17 cells and their related cytokines in a syngeneic model of PIOL, a subtype of non-Hodgkin lymphoma. The very small number of lymphocytes trafficking in normal eyes, which represent a low background as compared to tumor-bearing eyes, allows us to develop the present model to characterize the different lymphocyte subsets present when a tumor is developing. IL-21 mRNA was expressed concomitantly with IL-17 mRNA in tumor-bearing eyes and intracellular expression of IL-17A and IL-21 in infiltrating CD4+ T lymphocytes. Interestingly, IL-17A production by T cells was negatively correlated with tumor burden. We also showed that IL-21 but not IL-17 inhibits tumor cell proliferation in vitro.ConclusionsThese data demonstrate that IL-17A and IL-21-producing CD4+ T cells, referred as Th17 cells, infiltrate this tumor locally and suggest that Th17-related cytokines may counteract tumor progression via IL-21 production. Thus, Th17 cells or their related cytokines could be considered to be a new therapeutic approach for non-Hodgkin B-cell lymphomas, particularly those with an ocular localization.
Highlights
Non-Hodgkin’s lymphoma (NHL) is the major subtype of lymphoma and accounts for 3.4% of all cancer deaths [1]
These data demonstrate that IL-17A and IL-21-producing CD4+ T cells, referred as Th17 cells, infiltrate this tumor locally and suggest that Th17-related cytokines may counteract tumor progression via IL-21 production
Modulation of Th17 cells or administration of IL-21 alone could be considered as a new therapeutic approach for non-Hodgkin B-cell lymphomas, those with an ocular localization
Summary
Non-Hodgkin’s lymphoma (NHL) is the major subtype of lymphoma and accounts for 3.4% of all cancer deaths [1]. Few errant lymphocytes penetrate the eye in normal circumstances, it represents a small number of T cells This means that the present model makes it possible to monitor tumor-infiltrating lymphocytes (TIL), especially useful because the presence of immune cells in the B-cell lymphoma microenvironment has been reported to be a good prognostic indicator for patient survival [4]. Increasing evidence suggests that infiltration of IL-17-producing CD4+ T cells regulates tumor progression [6,7,8] These lymphocytes, called Th17 cells, usually produce IL-17, IL-21, and/or IL-22 [9], and help to clear pathogens [10]. Knowledge is sparse about the relation of Th17 to lymphoma microenvironments and, more to the microenvironment of primary intraocular B-cell lymphoma (PIOL), an aggressive lymphoma with a poor prognosis
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