Abstract
Purpose: :
To analyze the temporal development of lymphocytic infiltration in LHBETATAG retinal tumors. We propose to correlate tumor size with differential lymphocytic infiltration.
Methods: :
The study protocol was approved by the University of Miami, IACUC. All experiments were conducted in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. LHBETATAG mice (n=6 per group) of 4, 8, 12 and 16 weeks of age were analyzed. These age groups represent pre-neoplastic, small, medium and large tumors respectively. Eyes were assessed by immunohistochemistry for the presence of tumor CD4+ and CD8+ infiltrating lymphocytes.
Results: :
CD8+ lymphocytes are detected in small retinal tumors harbored by LHBETATAG mice. CD8+ staining is detected in the ganglion cell layer and Müller glia during early stages of tumor formation. Conversely, CD4+ staining is not detected until advanced disease. Results indicate a statistically significant increase in CD8+ and CD4+ lymphocyte infiltration associated with increased tumor burden in LHBETATAG retinal tumors (p<0.05). Both CD4+ and CD8+ lymphocytes co-localize with tumor vasculature in advanced disease.
Conclusions: :
Immunomodulatory activity of human retinoblastoma has been associated with tumor regression. A local inflammatory response has been detected following regression in these tumors. Previous studies have shown that in human retinoblastoma tumors, tumor infiltrating leukocytes can be activated to kill tumor cells (i.e., with IL-2). The presence of infiltrating CD4+ and CD8+ cells in retinal tumors from LHBETATAG transgenic mice provides a model for assessment of the role of immunomodulation in retinoblastoma tumor growth.
Keywords: retina • tumors • retinoblastoma