Tumor microenvironment and lymphoid tissues as two common tissue-level targets for the delivery of nucleic acid therapeutics in cancer immunotherapy. (A) The tumor microenvironment harbors a variety of cells including tumor cells, antigen presenting cells (DC, macrophage), lymphocytes (T cells, B cells and NK cells), and fibroblasts, which play a critical role in the development of tumor initiation, proliferation, as well as metastasis. (B) Lymphatic organs such as lymph nodes and spleen are among the desired sites for cancer therapeutics such as vaccines. DC: dendritic cells; TAM: tumor-associated macrophage; MDSC: myeloid-derived suppressor cells; NK cell: natural killer cell; APC: antigen-presenting cells; TGF-β: transforming growth factor-β; HGF: hepatocyte growth factor; MMP: matrix metalloproteinase.