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 mel anoma, were tested in vitro for susceptibility to NK cell-mediated lys is in the presence or absence of AH in conventional cytotoxicity assay s. Various numbers of RMA-S and OCM-3 tumor cells were injected either subcutaneously or intracamerally into C57BL/6 severe combined immunod eficiency mice and BALB/c nude mice respectively and tumor growth was monitored. The role of NK cell-mediated cytotoxicity in controlling tu mor growth was confirmed by depleting NK cells in severe combined immu nodeficiency mice by administering antiasialo GM1 antibodies before su bcutaneous tumor injection. Results. AH significantly inhibited NK cel l-mediated lysis of RMA-S and OCM-3 tumor cells in vitro and in vivo. NK sensitive RMA-S (1 x 10(4) cells) and OCM-3 tumors (1 x 10(6), 5 x 10(6) cells) were rejected after subcutaneous injection in C57BL/6 mic e, whereas the same or even lower numbers of cells grew progressively in the eye. In vivo NK cell depletion resulted in progressive growth o f 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 o f NK-sensitive intraocular tumors.