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Biomechanics in the tumor microenvironment: from biological functions to potential clinical applications
Hao Peng1,2, Zheng Chao1, Zefeng Wang3
1Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430300, China.
Abstract:
Immune checkpoint therapies have spearheaded drug innovation over the last decade, propelling cancer treatments toward a new era of precision therapies. Nonetheless, the challenges of low response rates and prevalent drug resistance underscore the imperative for a deeper understanding of the tumor microenvironment (TME) and the pursuit of novel targets. Recent findings have revealed the profound impacts of biomechanical forces within the tumor microenvironment on immune surveillance and tumor progression in both murine models and clinical settings. Furthermore, the pharmacological or genetic manipulation of mechanical checkpoints, such as PIEZO1, DDR1, YAP/TAZ, and TRPV4, has shown remarkable potential in immune activation and eradication of tumors. In this review, we delved into the underlying biomechanical mechanisms and the resulting intricate biological meaning in the TME, focusing mainly on the extracellular matrix, the stiffness of cancer cells, and immune synapses. We also summarized the methodologies employed for biomechanical research and the potential clinical translation derived from current evidence. This comprehensive review of biomechanics will enhance the understanding of the functional role of biomechanical forces and provide basic knowledge for the discovery of novel therapeutic targets.
Insights
Biomechanical forces in the tumor microenvironment significantly impact cancer progression and immune response. Targeting mechanical checkpoints offers a promising strategy for enhancing cancer therapies and overcoming drug resistance.
Area of Science:
- Oncology
- Immunology
- Biophysics
- Cancer Biology
Background:
- Immune checkpoint inhibitors have revolutionized cancer treatment, but challenges like low response rates and drug resistance persist.
- The tumor microenvironment (TME) plays a critical role in cancer progression and immune evasion.
- Emerging evidence highlights the significant influence of biomechanical forces within the TME on immune surveillance and tumor development.
Purpose of the Study:
- To review the biomechanical mechanisms within the TME and their biological implications.
- To explore the role of mechanical checkpoints (e.g., PIEZO1, DDR1, YAP/TAZ, TRPV4) in cancer immunity.
- To summarize research methodologies and discuss the clinical translation potential of biomechanical targeting in cancer therapy.
Main Methods:
- Literature review focusing on biomechanical forces in the TME.
- Analysis of studies investigating the impact of extracellular matrix, cancer cell stiffness, and immune synapses.
- Examination of research methodologies for biomechanical assessment and clinical translation strategies.
Main Results:
- Biomechanical forces profoundly affect immune surveillance and tumor progression.
- Manipulation of specific mechanical checkpoints (PIEZO1, DDR1, YAP/TAZ, TRPV4) shows potential for immune activation and tumor eradication.
- Understanding biomechanics is crucial for identifying novel therapeutic targets.
Conclusions:
- Biomechanical forces are integral to the TME's function and influence cancer treatment outcomes.
- Targeting mechanical pathways presents a promising avenue for novel cancer therapies.
- Further research into TME biomechanics can guide the development of more effective cancer treatments.
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