Extended Data Fig. 9: CCL22 mutations drive proliferation in vivo.

a,b, GFP positive cell rate in (a) spleen and (b) bone marrow cells at the end of study (batch 1; day 57, batch 2; day 44) in NSG mice (3 mice for each group) and NSG-Tg(Hu-IL15) mice that constitutively express human IL-15. Mice were transplanted with NK-92 cells expressing wild type (n = 3 (batch 1, square), 2 (batch 2, round), biologically independent animals) or mutant CCL22 (Pro79Arg; n = 3, 4), or GFP-expressing lentiviral vector (empty vector; n = 3, 4). NK-92 cells expressing mutant CCL22 showed higher GFP positive cell rate than wild type CCL22 and empty vector expressing NK-92 cells in both spleen and bone marrow. GFP positive cells were observed in NSG-Tg(Hu-IL15) mice but not or few in regular NSG mice. The mean GFP positive rate is shown by the dotted line. c,d, Peripheral blood analysis from retroorbital bleeds detected only few circulating human cells at week 6 (batch 2 day 44; the same day of the end of study, empty vector n = 4, wild type CCL22 n = 2, mutant CCL22 n = 4, biologically independent animal samples). Higher circulating human cells were observed in mutant CCL22 although at lower percentage than those observed in spleen and bone marrow. The mean (± SD) GFP positive rate is shown. P value was calculated by t-test. *0.01 < p < 0.05; **0.001 < p < 0.01; ***0.0001 < p < 0.001.