The antitumor effect of anti-JAML agonism is target dependent and requires the presence of both CD8 and γδ T cells. (A–F) Mice were challenged with B16F10 melanoma and treated with isotype IgG or anti-JAML antibodies on days 7, 10, and 13 after tumor challenge. (A and B) (A) Tumor growth in and (B) survival of WT versus Jaml^−/− mice (n = 11–15/group). (C and D) (C) Tumor growth in and (D) survival of WT versus Tcrd^−/− mice (n = 6–8/group). (E and F) (E) Tumor growth in and (F) survival of WT mice with or without CD8 T cell depletion (n = 9–11/group). Data in A–F represents a combined analysis of two independent experiments. Data in A, C, and E are expressed as mean ± SEM. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001; (A, C, and E) ANOVA with post hoc Tukey’s test or (B, D, and F) Kaplan-Meier log-rank P value.