Expression of CD94/NKG2 subtypes on tumor-infiltrating lymphocytes in primary and metastatic melanoma

Natural killer receptors are expressed both on natural killer populations a nd subpopulations of T cells, mainly alpha/beta TCR(+)CD8(+) T cells. We ha ve characterized the expression of the C-type lectin natural killer recepto r CD94/NKG2 on tumor-infiltrating lymphocytes in primary and metastatic mel anoma lesions. By immunohistochemistry, 5-10% of the tumor-infiltrating lym phocytes, both in primary and metastatic lesions, expressed CD94. More than 95% of these CD94(+) cells coexpressed CD8 and the percentage of CD94 expr ession within the CD8(+) cell population ranged from 5 to 20% with a higher expression in metastatic lesions. CD94/NKG2 exists both in an inhibitory a nd an activating form; thus, it was necessary to determine whether the inhi bitory CD94/NKG2-A/B, the activating CD94/NKG2-C/E, or both were expressed on tumor-infiltrating lymphocytes. Reverse transcription-polymerase chain r eaction using specific primers for NKG2-A/B and C/E mRNA revealed the prese nce of NKG2-C/E in all primary and metastatic lesions. In contrast, the inh ibitory NKG2-A/B was only present in 50% of primary tumors whereas 80% of t umor-infiltrating lymphocytes in metastatic lesions expressed these transcr ipts. In healthy humans, the mean number of inhibitory natural killer recep tors is higher than that of activating receptors, but the opposite was true for tumor-infiltrating lymphocytes in melanoma. The reversal of the ratio of inhibitory to activating natural killer receptors among tumor-infiltrati ng lymphocytes suggests a regulated event due to either specific factors wi thin the tumor microenvironment, preferential homing of T cell subsets, or certain stages of T cell activation.