New Immune Targets in Glioblastoma: CD44 and TNFSF14 Could Shape Future Treatments

Glioblastoma (GBM) remains one of the most aggressive and deadly brain cancers, with patients facing a median survival time of only around 15 months despite aggressive treatments like surgery, radiation, and chemotherapy. The limited success of current therapies and the tumor's ability to evade immune responses have posed significant challenges for clinicians and researchers alike.

A recent study published in Biomolecules and Biomedicine sheds new light on the immunosuppressive environment of GBM by identifying two key genes—CD44 and TNFSF14—that play vital roles in helping the tumor escape immune detection. Using a sophisticated network-based analysis focusing on PD-L1, a protein known for inhibiting immune activity in tumors, researchers found that both genes are consistently overexpressed in GBM compared to lower-grade gliomas and healthy brain tissue. The overexpression of CD44 and TNFSF14 was also strongly associated with poorer patient survival outcomes.

These findings were further validated through experimental analysis of human tumor samples, where the elevated levels of these genes distinguished GBM from normal brain tissue with high accuracy. Notably, their increased presence was particularly prominent in the mesenchymal subtype of GBM, known for its aggressive growth and resistance to treatment. Additionally, higher expression levels of CD44 and TNFSF14 correlated with increased infiltration of regulatory T cells and the presence of inactive natural killer cells, both markers of an immunosuppressed tumor microenvironment. Interestingly, CD44 showed a moderate positive correlation with PD-L1, linking it further to immune evasion pathways.

The research highlights the potential of targeting CD44 and TNFSF14 as part of the therapeutic strategy. CD44 is involved in tumor stem cell maintenance and invasiveness, while TNFSF14 may influence immune cell infiltration and checkpoint regulation. These genes could guide the development of more personalized and effective immunotherapies for GBM.

However, the authors emphasize that further functional studies are necessary, including gene knockout experiments and immune cell co-culture models, to better understand the precise role of these genes in immune suppression. Uncovering how CD44 and TNFSF14 modulate the tumor microenvironment provides promising avenues to overcome the current barriers in brain cancer treatment, aiming for therapies that can better stimulate the immune system against GBM.

This research offers valuable insights into the mechanisms behind GBM’s immune evasion and highlights new directions for developing targeted treatments that could improve patient outcomes in the future.

Source: https://medicalxpress.com/news/2025-06-immune-glioblastoma-cd44-tnfsf14-future.html