Human uveal melanoma cells produce macrophage migration-inhibitory factor to prevent lysis by NK cells

Human uveal melanoma arises in an immune privileged ocular environment in w hich both adaptive and innate immune effector mechanisms are suppressed. Uv eal melanoma is the most common intraocular tumor in adults and is derived from tissues in the eye that produce macrophage migration-inhibitory factor (MIF), a cytokine that has recently been demonstrated to produce immediate inhibition of NK cell-mediated lytic activity. Although NK cell-mediated l ysis of uveal melanomas is inhibited in the eye, melanoma cells that dissem inate from the eye are at risk for surveillance by NK cells. Moreover, uvea l melanoma cells demonstrate a propensity to metastasize to the liver, an o rgan with one of the highest levels of NK activity in the body. Therefore, we speculated that uveal melanomas produced MIF as a means of escaping NK c ell-mediated lysis, Accordingly, seven primary uveal melanoma cell lines an d two cell lines derived from uveal melanoma metastases were examined for t heir production of MIF, MIF was detected in melanoma culture supernatants b y both ELISA and the classical bioassay of macrophage migration inhibition. Melanomaderived MIF inhibited NK cell-mediated lysis of YAC-1 and uveal me lanoma cells. Cell lines derived from uveal melanoma metastases produced ap proximately twice as much biologically active MIF as cultures from primary uveal melanomas, Inhibition of NK cell-mediated killing by uveal melanoma-d erived MIF was specifically inhibited in a dose-dependent manner by anti-MI F Ab, The results suggest that human uveal melanoma cells maintain a microe nvironment of immune privilege by secreting active MIF that protects agains t NK cell-mediated killing.