Tumor cell death by pattern-sensing of exogenous RNA: Tumor cell TLR3 directly induces necroptosis by poly(I:C) in vivo, independent of immune effector-mediated tumor shrinkage

Figures & data

Figure 1. PolyI:C induces tumor necroptosis via the TLR3 -TICAM1 pathway. When CT26 cells are treated with pan-caspase inhibitor, zVAD, the interaction of TICAM1 and RIP3 is enhanced in response to poly(I:C), leading to cell death by necroptosis. In the absence of immune cells, this necroptosis pathway contributes to tumor regression in vivo. Necroptosis is induced in macrophages stimulated with poly(I:C).² Poly(I:C) also acts on DCs and macrophages to elicit effective CTL/NK activation and modify tumor microenvironment, respectively, as previously reported.^4-6 The antitumor response of TLR3 appears to be cell type-specific. Notably, tumor-infiltrated macrophages harbor all the signal axes inducible by poly(I:C)/TLR3 as illustrated. The functional alteration of macrophages may be associated with epigenetic status of the cells in inflammatory environment.

Jouan-Lanhouet S, Riquet F, Duprez L, Vanden Berghe T, Takahashi N, Vandenabeele P. Necroptosis, in vivo detection in experimental disease models. Semin Cell Dev Biol 2014; 35:2-13; PMID:25160988; https://doi.org/10.1016/j.semcdb.2014.08.010

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