『Cover Story』Deciphering the tumor microenvironment: how RNA-RNA binding proteins reveal new targets for the treatment of IDH wild-type glioblastoma!

Volume 26 lssue 6,June 2024

Wu Lele, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore

Cover design process

First of all, in terms of design ideas, the cover succeeds in presenting the complex scientific theme in a visual way. The multicolored cell image at the center immediately captures the viewer's attention, not only demonstrating the complex structure and function of the cell interior, but also suggesting the dynamic and complex nature of the tumor microenvironment.

In terms of modeling sophistication, this cover demonstrates excellent detailing. These cellular structures and details not only reflect the rigor and precision of scientific research, but also enhance the visual impact and appeal of the cover. In addition, the yellow dots in the image have been carefully designed to highlight a specific area or structure within the cell.

Overall, the cover image successfully conveys the scientific value and importance of the research topic through unique design ideas, detailed modeling, and harmonious color combinations. It not only demonstrates the fascination and depth of scientific research, but also provides readers with an unforgettable visual experience. Eventually the cover was highly recognized by the teachers and journal editors, and successfully published in the journal!

The cover of this issue of Nature Cell Biology is “Tumour microenvironment programming by an RNA-RNA-binding protein complex creates a druggable vulnerability in IDH-wild-type glioblastom” by Prof. Vinay Tergaonkar of the Institute of Molecular and Cellular Biology (IMCB) of the Agency for Science and Technology Research (ASTR), Singapore, and Academician Jiang Tao of the Tiantan Hospital, Beijing.

Background of the study

IDH wild-type glioblastoma (GBM) is a highly malignant brain tumor with an extremely low long-term survival rate for its patients. Current first-line treatments, such as surgical resection, radiotherapy, and chemotherapy, can control the disease to a certain extent, but the overall effect is limited and treatment resistance is common. Therefore, the search for novel factors and mechanisms that modulate the infiltration of GAMs is crucial for the development of new therapeutic approaches.Research significance In this study, by deeply analyzing the immune microenvironment of GBM, we identified a unique RNA:RBP complex—— LOC:DHX15, which plays a key role in the disease progression of IDH wild-type GBM. 

Significance of the study

In this study, by deeply analyzing the immune microenvironment of GBM, we identified a unique RNA:RBP complex, LOC:DHX15, which plays a key role in the disease progression of IDH wild-type GBM. The complex reprograms the tumor microenvironment by regulating the interactions between tumor cells and macrophages, thereby affecting tumor growth and progression. What's more, it was noted that targeting the complex significantly reduces tumor-associated macrophage infiltration and improves the response rate to the standard treatment temozolomide (TMZ). This finding not only provides new ideas for the treatment of GBM, but also provides new insights into the critical role of RNA and RNA-binding proteins in the regulation of the tumor immune microenvironment.

Research Outlook

1. Innovation of therapeutic strategies:

This study proposes an RNA-based:RBPs complexes proposed in this study opens up new directions for the treatment of GBM. Compared with the traditional protein-targeting strategy, RNA and RBPs have a larger chemical space and lower immunogenicity as drug targets, which offers the possibility of developing novel drugs.

2. In-depth investigation of the mechanism:

Although this study has revealed the mechanism of action of the LOC:DHX15 complex in GBM, there are still many details that need to be further explored. For example, how the complex specifically regulates the interactions between tumor cells and macrophages, and the role of the complex in other types of tumors. The in-depth exploration of these mechanisms will help us better understand the regulatory mechanisms of the tumor immune microenvironment and provide theoretical support for the development of more effective therapeutic strategies.

3. Extension of clinical application:

This study validated the therapeutic efficacy of targeting LOC:DHX15 complex in a preclinical mouse model, but further clinical trials are needed to verify its safety and efficacy. In the future, we expect to see more therapeutic agents based on RNA:RBPs complexes enter clinical trials, bringing hope to GBM patients.

4. Development of novel therapeutic strategies:

With the increasing understanding of the role of RNAs and RBPs in the regulation of the tumor immune microenvironment, we expect to develop more novel therapeutic strategies based on RNAs and RBPs. These strategies may include, but are not limited to, RNA interference, RNA mimics, RBP inhibitors, etc., which will provide more choices for the treatment of GBM, as well as for the treatment of other types of tumors.