Targeting RNA N6-methyladenosine to synergize with immune checkpoint therapy

Abstract

Cancer immunotherapy, especially immune checkpoint therapy, has revolutionized therapeutic options by reactivating the host immune system. However, the efficacy varies, and only a small portion of patients develop sustained antitumor responses. Hence, illustrating novel strategies that improve the clinical outcome of immune checkpoint therapy is urgently needed. N6-methyladenosine (m6A) has been proved to be an efficient and dynamic posttranscriptional modification process. It is involved in numerous RNA processing, such as splicing, trafficking, translation and degradation. Compelling evidence emphasizes the paramount role of m6A modification in the regulation of immune response. These findings may provide a foundation for the rational combination of targeting m6A modification and immune checkpoints in cancer treatment. In the present review, we summarize the current landscape of m6A modification in RNA biology, and highlight the latest findings on the complex mechanisms by which m6A modification governs immune checkpoint molecules. Furthermore, given the critical role of m6A modification in antitumor immunity, we discuss the clinical significance of targeting m6A modification to improve the efficacy of immune checkpoint therapy for cancer control.

Chemically Modified Platforms for Better RNA Therapeutics

“…Moreover, m6A modification affects mRNA stability, localization, nuclear export, splicing, and translation. RNA immunoprecipitation assay has been employed to demonstrate the modification of m6A on PD-L1 mRNA, providing a means to regulate PD-L1 expression through RNA modification. − m6A modification has also been introduced into the mRNA of TLR4, leading to increased translation and down-regulated degradation, resulting in elevated protein levels and improved TLR4 signaling activation of neutrophils . The use of the pseudouridine and m5C-modified RALA mRNA nanocomplex has been shown to enhance the potency of cytolytic T cell responses .…”

Cocktail Cell‐Reprogrammed Hydrogel Microspheres Achieving Scarless Hair Follicle Regeneration

“…It has been widely reported that liposome is an ideal platform for fat-soluble drug loading and slow release. [27] Hyaluronic acid and gelatin, as the major component of ECM, have proven effective in regulating key cellular processes and behaviors, including proliferation, differentiation, and the inflammatory response, [28] which may contribute to cellular reprogramming. [29] Adhesive seed microsphere AFHS with TiT cocktail nucleus and positively charged surface modification were developed through liposome nanodrug carrier system, microfluidic technology, photoresponsive crosslinking technology, and poly allylamine hydrochloride (PAH) activation (Figure 2f).…”

Targeting the NF-κB pathway as a potential regulator of immune checkpoints in cancer immunotherapy

“…NF-κB complexes containing c-Rel subunits essentially contribute in the immune response and lymphoid development. Considering the dual role of NF-κB in inducing an antitumor immune response against cancerous cells, and inducing the expression of immune checkpoints in Treg cells, employment of NF-κB suppressors for cancer immunotherapy is challenging [ 143 , 144 ]. It has been suggested that the use of inhibitors that target only the NF-κB c-Rel subunit could open a new avenue in cancer treatment [ 145 ].…”