Abstract
Cancer immunotherapy especially immune checkpoint inhibition has achieved unprecedented successes in cancer treatment. However, there are many patients who failed to benefit from these therapies, highlighting the need for new combinations to increase the clinical efficacy of immune checkpoint inhibitors. In this review, we summarized the latest discoveries on the combination of nucleic acid-sensing immunity and immune checkpoint inhibitors in cancer immunotherapy. Given the critical role of nuclear acid-mediated immunity in maintaining the activation of T cell function, it seems that harnessing the nuclear acid-mediated immunity opens up new strategies to enhance the effect of immune checkpoint inhibitors for tumor control.
Highlights
Cancer immunotherapy, exploiting to activate the immune system to fight malignancies, has become a major strategy for a long time
The most commonly used strategy is the inhibition of immune checkpoints, targeting the programmed cell death receptor-1 (PD-1), and its ligand, programmed cell death ligand-1 (PD-L1) and cytotoxic T lymphocyte-associated protein 4 (CTLA4).[2]
It’s inspiring that the agonists of TLR9, CMP-001, and SD-101, could stimulate TLR9 and induce plasmacytoid DCs (pDCs) to secrete type I IFNs and inflammatory chemokines, and facilitate cytotoxic T cells infiltration to potentially overcome the resistance of PD-1 blockade in metastatic melanoma patients.[110–112]
Summary
Cancer immunotherapy, exploiting to activate the immune system to fight malignancies, has become a major strategy for a long time. CMP-001, another agonist of TLR9 can facilitate the anti-tumor immune response including the increased expression of chemokines, pro-inflammatory cytokines, and the infiltration of CD8+ T and NK cells, which improves the survival in colon carcinoma and pancreatic cancer.[109]. It’s inspiring that the agonists of TLR9, CMP-001, and SD-101, could stimulate TLR9 and induce pDCs to secrete type I IFNs and inflammatory chemokines, and facilitate cytotoxic T cells infiltration to potentially overcome the resistance of PD-1 blockade in metastatic melanoma patients.[110–112] In the small cell lung cancer mouse model, PARP or CHK1 inhibition significantly potentiated the anti-tumor effect of PD-L1 blockade via STING mediated IRF3 activation, thereby inducing type I IFNs production and innate immune activation.[139].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
