Key questions about the checkpoint blockade-are microRNAs an answer?

Mihnea Dragomir, et al.


The introduction of immune-checkpoint blockade in the cancer therapy led to a paradigm change of the management of late stagecancers. There are already multiple FDA approved checkpoint inhibitors and many other agents are undergoing phase 2 and earlyphase 3 clinical trials. The therapeutic indication of immune checkpoint inhibitors expanded in the last years, but still remainsunclear who can benefit. MicroRNAs are small RNAs with no coding potential. By complementary pairing to the 3' untranslatedregion of messenger RNA, microRNAs exert posttranscriptional control of protein expression. A network of microRNAs directlyand indirectly controls the expression of checkpoint receptors and several microRNAs can target multiple checkpoint molecules,mimicking the therapeutic effect of a combined immune checkpoint blockade. In this review, we will describe the microRNAs thatcontrol the expression of immune checkpoints and we will present four specific issues of the immune checkpoint therapy incancer: (1) imprecise therapeutic indication, (2) difficult response evaluation, (3) numerous immunologic adverse-events, and (4)the absence of response to immune therapy. Finally, we propose microRNAs as possible solutions for these pitfalls. We considerthat in the near future microRNAs could become important therapeutic partners of the immune checkpoint therapy.


MicroRNA; PD-1; PD-L1; CTLA-4; checkpoint inhibitors

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