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Basic science and clinical investigations in cancer research have contributed to our understanding of the genetic causes of various neoplasms and discovery of novel therapeutic interventions to fight malignancies such as lymphoma. During this exciting time, we have witnessed the advent of new technologies to further characterize primary intraocular lymphoma (PIOL), or retinal lymphoma, which is selected as the first “Disease of the Year” by Ocular Immunology and Inflammation. Different comprehensive aspects of PIOL, including epidemiology, clinical manifestations, diagnosis, pathophysiology, therapy, and animal models are discussed. The future of PIOL holds an opportunity to really understand the unique cytologic, histopathologic, physiological and immunologic features, as well as the genotypic traits (gene expression, interaction, polymorphism, epigenetics, etc.) and epidemiology. This information will empower us to truly make a difference in patients’ managements with this devastating disease. While most of this technology already exists, much work still needs to be done to make translational therapy a reality for PIOL patients in the future. [ABSTRACT FROM AUTHOR]

Background: Toll-like receptor (TLR) agonists have important properties that can be exploited for immunotherapy against tumors. Locally injected immunostimulatory oligodeoxynucleotides containing CpG motifs (CpG-ODNs), which are TLR9 agonists, have shown promise in cancer models. Several studies have demonstrated that these motifs have immunologic effects similar to those of bacterial DNA and can stimulate monocytes, macrophages, dendritic, and B cells, which then produce several proinflammatory cytokines. However, these CpG-ODNs appear to produce opposite effects on tumor B cells. Methods: In this study, we investigated the direct effects of a murine class B CpG (1826) ODNs on lymphoma B cells in vitro and in vivo, using mouse models of non-Hodgkin B lymphomas developing in immunoprivileged sites, specifically the brain and the eye, and in subcutaneous sites. Results: In vitro, CpG-ODNs produced antiproliferative and proapoptotic effects on lymphoma B cells. In vivo, it had an antitumor effect when injected into tumors in murine models of subcutaneous lymphoma (SCL) and primary cerebral lymphoma (PCL). However, its intravitreal administration into a primary intraocular lymphoma (PIOL) mouse model did not produce an antitumor effect. In vitro experiments using supernatant from mouse PIOL samples demonstrated that the PIOL molecular microenvironment inhibits the antiproliferative effect of CpG-ODNs on lymphoma B-cells. Conclusions: Responsiveness to CpG stimulation differs in subcutaneous, cerebral, and ocular tumors, according to the tumoral and molecular microenvironment, and this should be considered for further therapeutic approaches. [ABSTRACT FROM AUTHOR]

Primary intraocular lymphoma is a high-grade non-Hodgkin lymphoma whose pathogenesis is still unclear. Few animal models exist in order to study this condition. Although intraocular lymphomas in humans are usually B cell lymphomas, most of these models are T cell lymphomas. Recently, a major step forward has been realized with the development of new models of intraocular B cell lymphoma. New therapeutic tools are being evaluated in these models of B cell lymphoma. We evaluate the contribution of the different animal models available to study intraocular lymphomas, and we discuss the new therapeutic strategies and their various targets in the tumor as well as in the environment, which are currently investigated through the development of these models. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]