Fig. 3

RNA-based modulation of the TIME and immunotherapy. Effector T cells, which play an important role in the antitumor immune response, can be targeted by different kinds of in vitro-transcribed RNA aptamers such as bispecific, antagonist, and chimeric. The interaction of these aptamers helps to prolong survival and inhibits T cell exhaustion that is linked with upregulation of antitumor immunity. Blocking immunosuppression-associated molecules using ASOs is another approach for cancer immunotherapy. Targeting immunosuppressor and immune-evading molecules such as CD47, TGF-β, CTLA-4, and CSF-1R by delivering their specific siRNAs in the form of NPs could lead to strong antitumor immune response. CD39 ASO downregulates CD39 expression on Tregs and TAMs, which are responsible for conversion of immunostimulating ATP into the immunosuppressive molecule adenosine. Modulating the function of MDSCs using STAT3 ASO results in the recruitment of higher levels of cytotoxic T cells. Targeting MTDH in the tumor cells with ASOs promotes antitumor immune response. Activating the tumor suppressor genes such as PTEN using PTEN mRNA-loaded NPs helps to inhibit the tumor growth by downregulating MDSCs and Tregs and activating CD8 + T cells. TGF-β, transforming growth factor-β; TNF-α, tumor necrosis factor α; INF-γ, Interferon gamma; IL, interleukin; IL-10R, interleukin-10 receptor; PSMA, prostate-specific membrane; LAG3, lymphocyte activation gene 3 protein; PD-1, programmed cell death protein 1; TIM3, T cell immunoglobulin mucin receptor 3; CSF-1R, colony-stimulating factor 1 receptor; ATP, adenosine triphosphate