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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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Updated: Oct 31, 2025

Isolation of Proximal Fluids to Investigate the Tumor Microenvironment of Pancreatic Adenocarcinoma
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Pancreatic Tumor Microenvironment.

Kai Wang1, Hong He2

  • 1Department of Surgery, University of Melbourne, Austin Health, Heidelberg, VIC, Australia.

Advances in Experimental Medicine and Biology
|June 29, 2021
PubMed
Summary
This summary is machine-generated.

Reprogramming the pancreatic ductal adenocarcinoma (PDAC) stroma, rather than depleting it, offers new therapeutic strategies. Targeting pancreatic stellate cells (PSCs) and immune infiltration can reprogram the tumor microenvironment (TME) for better pancreatic cancer treatment.

Keywords:
Alpha-smooth muscle actin (α-SMA)CollagensCytotoxic T cellsExtracellular matrix (ECM)GemcitabineHypoxiaHypoxia-inducible factors (HIFs)Immune checkpoint proteinsMyeloid-derived suppressor cells (MDSCs)Pancreatic ductal adenocarcinoma (PDAC)Pancreatic stellate cells (PSCs)Tumor immune responseTumor infiltrating lymphocytes (TILs)Tumor microenvironment (TME)Tumor-associated macrophages (TAMs)

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Area of Science:

  • Oncology
  • Cancer Biology
  • Immunology

Background:

  • The pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME) is characterized by a dense, desmoplastic stroma.
  • This stroma, rich in pancreatic stellate cells (PSCs) and immunosuppressive immune cells like M2 macrophages, creates a pro-tumorigenic environment.
  • The fibrotic stroma acts as a barrier, hindering the delivery of cytotoxic agents and limiting T-cell infiltration, thereby promoting tumor progression and chemoresistance.

Purpose of the Study:

  • To explore therapeutic strategies for pancreatic cancer by focusing on reprogramming the PDAC tumor microenvironment (TME).
  • To investigate the potential of modulating pancreatic stellate cells (PSCs) and immune cell infiltration within the TME.

Main Methods:

  • Analysis of the PDAC tumor microenvironment (TME), including its stromal and immune cell components.
  • Review of existing literature on the role of pancreatic stellate cells (PSCs), fibrosis, and immune cells (e.g., macrophages) in PDAC progression.
  • Evaluation of the effects of stroma depletion versus reprogramming in preclinical models.

Main Results:

  • The desmoplastic stroma in PDAC, driven by PSCs and immunosuppressive cells, impedes anti-tumor immunity and chemotherapy efficacy.
  • Experimental depletion of the stroma has paradoxically led to more aggressive cancer in animal studies.
  • Modulating PSCs/fibrosis and immune infiltration/inflammation are key aspects of TME reprogramming.

Conclusions:

  • Reprogramming the PDAC stroma, rather than its depletion, holds significant potential for developing novel therapeutic strategies.
  • Targeting pancreatic stellate cells (PSCs) and modulating immune responses within the TME are crucial for effective pancreatic cancer treatment.