Extracellular matrix and tumor-immune interactions: challenges & opportunities

“This review explores our current understanding of how ECM geometry influences the behaviors of both immune cells and tumor cells, which in turn impacts treatment efficacy and cancer evolutionary progression.”

BUFFALO, NY - November 12, 2024 – A new review was published in Oncotarget's Volume 15 on November 7, 2024, entitled “Understanding the interplay between extracellular matrix topology and tumor-immune interactions: Challenges and opportunities.”

This comprehensive review by researchers Yijia Fan, Alvis Chiu, Feng Zhao, and Jason T. George from Texas A&M University, Rice University, and MD  Anderson Cancer Center sheds light on how the structural properties of the extracellular matrix (ECM) within tumors impact immune cell behavior and influence the effectiveness of cancer immunotherapies. The ECM, a network of proteins surrounding cells, often transforms in cancer, becoming denser and more aligned. These changes create physical barriers that can prevent immune cells, especially T cells, from effectively accessing and attacking tumors, thereby limiting the success of immunotherapies.

The team emphasizes the role of specific ECM configurations, known as Tumor-Associated Collagen Signatures (TACS), in cancer progression and immune evasion. TACS1 and TACS2 patterns create "immune deserts" around tumors, limiting immune cell movement and preventing T cells from recognizing and attacking cancer cells, which is essential for successful immunotherapy. In advanced stages, TACS3 aligns ECM fibers in ways that both promote tumor spread and create additional barriers, further obstructing immune cell access to the tumor.

These insights lead the way for ECM-targeted therapies designed to modify these barriers, potentially transforming “cold” (immune-non-responsive) tumors into “hot” (immune-responsive) ones, thereby improving immune cell infiltration and enhancing treatment outcomes.

“Understanding the complex interplay is relevant for developing more accurate model of tumor evasion and the identification of corresponding therapeutic intervention.”

The review highlights advanced computational models that simulate interactions between the ECM, immune cells, and tumors, offering valuable insights for developing ECM-targeted therapies. These models illustrate how modifying ECM properties could enhance immune cell migration and function, potentially overcoming immune resistance and expanding the effectiveness of immunotherapies.

The authors also suggest that targeting ECM structure could significantly enhance the effectiveness of immunotherapy, especially for cancers like breast, pancreatic, and ovarian, which often feature dense ECM regions. By reshaping the ECM, such treatments could enable immune cells to access previously unreachable tumor areas, presenting a promising strategy to combat tumors that are resistant to standard therapies.

In conclusion, the review underscores the need for continued research into ECM-focused strategies, which could support more integrated approaches to cancer treatment. By targeting the ECM’s physical barriers and immune evasion mechanisms, these strategies hold promise for improving outcomes in difficult-to-treat cancers.

Continue reading: DOI: https://doi.org/10.18632/oncotarget.28666

Correspondence to: Jason T. George - jason.george@tamu.edu

Keywords: ECM; tumor-T cell evolution; tumor microenvironment

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