Local inhibition of natural killer cell activity promotes the progressive growth of intraocular tumors

Purpose. To study the effect of aqueous humor (AH)-mediated inhibition of natural killer (NK) cell activity on intraocular tumor progression. Methods. Two NK-sensitive tumors, RMA-S lymphoma and OCM-3 uveal melanoma, were tested in vitro for susceptibility to NK cell-mediated lysis in the presence or absence of AH in conventional cytotoxicity assays. Various numbers of RMA-S and OCM-3 tumor cells were injected either subcutaneously or intracamerally into C57BL/6 severe combined immunodeficiency mice and BALB/c nude mice respectively and tumor growth was monitored. The role of NK cell- mediated cytotoxicity in controlling tumor growth was confirmed by depleting NK cells in severe combined immunodeficiency mice by administering anti- asialo GM1 antibodies before subcutaneous tumor injection. Results. AH significantly inhibited NK cell-mediated lysis of RMA-S and OCM-3 tumor cells in vitro and in vivo. NK sensitive RMA-S (1 x 10⁴ cells) and OCM-3 tumors (1 x 10⁶, 5 x 10⁶ cells) were rejected after subcutaneous injection in C57BL/6 mice, whereas the same or even lower numbers of cells grew progressively in the eye. In vivo NK cell depletion resulted in progressive growth of subcutaneously injected RMA-S tumors at a dose rejected by mice with normal NK cell activity. Conclusions. AH inhibits NK cell activity in vitro and within the interior of the eye and prevents the rejection of NK-sensitive intraocular tumors.