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The Tumor Microenvironment02:17

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Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
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Targeting extracellular matrix stiffness for cancer therapy.

Xiuqin Feng1, Fujun Cao1, Xiangji Wu1

  • 1Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Frontiers in Immunology
|December 19, 2024
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Tumor stiffness impedes drug delivery and immune cell infiltration, hindering effective cancer immunotherapy. Modulating tumor mechanical properties offers a promising strategy to enhance treatment efficacy in solid tumors.

Keywords:
immunotherapymatrix stiffnessmechanical propertiessolid tumorstumor microenvironment

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Area of Science:

  • Oncology
  • Biophysics
  • Immunology

Background:

  • The tumor microenvironment (TME) exhibits physical characteristics like solid stress, interstitial fluid pressure, and tissue stiffness.
  • Abnormal tissue stiffness in the TME negatively impacts drug delivery and immune cell infiltration.
  • Increased tumor stiffness is associated with resistance to immunotherapy.

Purpose of the Study:

  • To review the mechanical properties of tumors.
  • To discuss the impact of a stiff TME on tumor and immune cells.
  • To explore strategies for modulating tumor mechanics to improve immunotherapy.

Main Methods:

  • Literature review of studies on tumor physical characteristics.
  • Analysis of the effects of tissue stiffness on cellular infiltration and drug delivery.
  • Examination of therapeutic strategies targeting tumor mechanics.

Main Results:

  • Tissue stiffness is a critical physical characteristic of the TME.
  • A stiff TME poses significant barriers to effective drug delivery and immune cell infiltration.
  • Tumor stiffness contributes to resistance against immunotherapies.

Conclusions:

  • Targeting and modulating tumor tissue stiffness can enhance drug and immune cell infiltration.
  • Strategies aimed at altering the mechanical properties of the TME hold potential for improving immunotherapy efficacy in solid tumors.