The disclosure provides compositions and methods for inducing tripartite motif-containing protein 16 (TRIM 16) activity in a cell. This activity can manifest in programmed cell death in cancer cells. The compositions comprise pathogen-associated molecular pattern (PAMP)-containing nucleic acid molecule. The PAMP-containing molecule can comprise a 5'-arm region comprising a terminal triphosphate, a poly-uracil core comprising at least 8 contiguous uracil residues, and a 3'-arm region comprising at least 8 nucleic acid residues, wherein the 5'-most nucleic acid residue of the 3'-arm region is not a uracil and wherein the 3'-arm region is at least 30% uracil residues. The compositions can be combined with or used in combination with other cancer therapeutics, including in combination with additional immunotherapeutics.
