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Related Concept Videos

The Tumor Microenvironment02:17

The Tumor Microenvironment

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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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Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
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Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
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Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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Updated: Sep 19, 2025

Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells
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NK cell activity in the tumor microenvironment.

A V Kuznetsova1,2, X A Glukhova3, I P Beletsky3

  • 1Laboratory of Molecular and Cellular Pathology, Russian University of Medicine, Ministry of Health of the Russian Federation, Moscow, Russia.

Frontiers in Cell and Developmental Biology
|June 16, 2025
PubMed
Summary

The tumor microenvironment (TME) suppresses natural killer (NK) cell therapy. Modulating the extracellular matrix (ECM) in the TME can improve NK cell function and enhance cancer immunotherapy efficacy.

Keywords:
anti-NK cell signalingextracellular matrixhuman natural killer cellsnew targetstumor microenvironment

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Area of Science:

  • Immunology
  • Oncology
  • Biophysics
  • Materials Science
  • Nanotechnology

Background:

  • The tumor microenvironment (TME) creates an immunosuppressive state that hinders natural killer (NK) cell infiltration, persistence, and cytotoxic activity, limiting the effectiveness of NK cell-based cancer immunotherapies, particularly in solid tumors.
  • Current therapeutic strategies focus on overcoming tumor immune evasion by boosting NK cell recognition, cytotoxicity, and resistance to the TME, alongside enhancing their infiltration and persistence.

Purpose of the Study:

  • This review examines the biophysical properties of the TME and extracellular matrix (ECM) components that impact NK cell function.
  • The study aims to identify therapeutic strategies for modulating the TME to establish a more supportive environment for adaptive immune cell activity.

Main Methods:

  • Review of existing literature on the TME, ECM, NK cell biology, and cancer immunotherapy.
  • Analysis of biophysical characteristics of the TME and their influence on NK cell function.
  • Exploration of interdisciplinary approaches involving oncology, cell biology, physics, engineering, materials science, and nanotechnology.

Main Results:

  • The TME's biophysical characteristics, including ECM rigidity, significantly impede NK cell-mediated anti-tumor responses.
  • Specific ECM components and mechanotransduction signaling pathways within the TME play critical roles in regulating NK cell activity.
  • Interdisciplinary research is essential for developing novel therapeutic interventions.

Conclusions:

  • Targeting the biophysical properties of the TME, particularly ECM rigidity and associated signaling pathways, holds promise for enhancing NK cell therapy efficacy.
  • Creating a permissive TME through targeted interventions can improve NK cell infiltration, persistence, and cytotoxic function, thereby advancing cancer immunotherapy.
  • Collaborative efforts across multiple scientific disciplines are vital for translating these findings into effective clinical strategies.