Human cells contain two types of adenosine deaminases (ADA) each with unique properties: ADA1, which is present in all cells where it modulates intracellular functions and extracellular signaling, and ADA2, which is secreted by immune cells. The exact intracellular functions of ADA2 remain undetermined and less defined than those of ADA1. ADA2 has distinct characteristics, such as low adenosine affinity, heparin-binding ability, and putative lysosomal entry. Here, we confirm that ADA2 is a lysosomal protein that binds toll-like receptor 9 (TLR9) agonists, specifically CpG oligodeoxynucleotides (CpG ODNs). We show that interferon-alpha (IFN-α) is secreted in response to TLR9 activation by CpG ODNs and natural DNA and markedly increases when ADA2 expression is downregulated in plasmacytoid dendritic cells (pDCs). Additionally, the pretreatment of pDCs with RNA further stimulates IFN-α secretion by pDCs after activation with CpG ODNs. Our findings indicate that ADA2 regulates TLR9 responses to DNA in activated pDCs. In conclusion, decreasing ADA2 expression or blocking it with specific oligonucleotides can enhance IFN-α secretion from pDCs, improving immune responses against intracellular infections and cancer.

This review is the first to provide a comprehensive overview of the latest advancements in metastatic brain tumors. Professor Rongrong Zhou and colleagues not only highlight preclinical progress, such as the development of model systems and exploration of underlying mechanisms, but also offer a thorough summary of the evolution of various clinical therapies and cutting-edge treatments. Additionally, the integration of multi-omics technologies in the modern era is depicted, shedding new light on the intricate landscape of brain metastasis and unveiling its mystery.

A multicenter phase II trial has demonstrated that a combination of pyrotinib and fulvestrant offers significant antitumor activity and acceptable safety for hormone receptor-positive (HR+)/HER2-positive metastatic breast cancer patients who have developed resistance to trastuzumab. The study revealed a median progression-free survival (PFS) of 18.2 months and a disease control rate (DCR) of 97.5%, highlighting a novel therapeutic strategy for this challenging patient population.A multicenter phase II trial has demonstrated that a combination of pyrotinib and fulvestrant offers significant antitumor activity and acceptable safety for hormone receptor-positive (HR+)/HER2-positive metastatic breast cancer patients who have developed resistance to trastuzumab. The study revealed a median progression-free survival (PFS) of 18.2 months and a disease control rate (DCR) of 97.5%, highlighting a novel therapeutic strategy for this challenging patient population.

Researchers at Tel Aviv University have developed a new platform using polymeric nanoparticles to deliver drug pairs to specific cancer types, including skin cancer and breast cancer. The researchers explain that having both drugs arrive at the tumor site together significantly amplifies their therapeutic effects and safety profiles.