Fig. 4. CD4+ effector T cells cooperate with activated iNOS-expressing tumouricidal monocytes and macrophages to orchestrate remote inflammatory cell death of MHC-deficient and IFN-unresponsive tumours.
a, Graphical representation of interaction phenotypes of indicated HCmel12 variants. b, Experimental treatment protocol to study the impact of chemical iNOS inhibition using L-NIL on CD4 ACT-mediated tumour control. c, Kaplan–Meier survival graphs of mice bearing established HCmel12 Ciita-KO melanomas (left) or HCmel12 Jak1-KO melanomas (right) and treated as indicated (NT, non-treated; CR, complete responders; **P = 0.0033). Survival was statistically compared using a log-rank Mantel–Cox test. Means between groups were statistically compared using a one-way ANOVA with Tukey post hoc. d, Experimental protocol to assess the ability of the inflammatory mediators TNF, IFNγ and the nitric oxide donor SNAP to induce melanoma cell death. e,f, Percentage of cell death in mouse (e) and human (f) melanoma cells treated as indicated (mean ± s.e.m. from 2–3 technical replicates). g, Graphical summary of inflammatory cell death induction of MHC-deficient and IFN-unresponsive tumours by CD4+ T cells in cooperation with iNOS-expressing myeloid cells.