Related Experiment Video

Updated: Aug 29, 2025

Flow Cytometry-Based Isolation and Therapeutic Evaluation of Tumor-Infiltrating Lymphocytes in a Mouse Model of Pancreatic Cancer
07:55

Flow Cytometry-Based Isolation and Therapeutic Evaluation of Tumor-Infiltrating Lymphocytes in a Mouse Model of Pancreatic Cancer

Published on: January 17, 2025

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Nucleolin Therapeutic Targeting Decreases Pancreatic Cancer Immunosuppression

Matteo Ponzo1, Anais Debesset1, Mélissande Cossutta1

  • 1Immune Regulation and Biotherapy, Inserm U955, IMRB University of Paris-Est Creteil (UPEC) 8, INSERM, IMRB, F-94010 Créteil, France.

Cancers
|September 9, 2022
PubMed

Insights

Nucleolin (NCL) inhibition with N6L combats pancreatic cancer by reducing immunosuppressive cells and boosting T cell activity. This approach targets the tumor stroma, offering a novel therapeutic strategy for pancreatic ductal adenocarcinoma.

Area of Science:

  • Oncology
  • Immunology
  • Cancer Biology

Background:

  • Pancreatic ductal adenocarcinoma (PDAC) features a fibrotic, hypoxic tumor microenvironment hindering immune cell infiltration.
  • Previous research indicated nucleolin (NCL) inhibition normalizes tumor vasculature and impedes PDAC growth.

Purpose of the Study:

  • To investigate the effects of NCL inhibition on the PDAC immune microenvironment and identify underlying mechanisms.
  • To evaluate the therapeutic potential of NCL inhibition in preclinical models of PDAC.

Main Methods:

  • Immunocompetent mouse models of PDAC were treated with the NCL-inhibiting pseudopeptide N6L.
  • Analysis of tumor-infiltrating immune cells, tumor microenvironment changes, and gene expression (RNAseq) was performed.
  • Comparative studies included anti-VEGFR2 treatment and IL-6 blockade.

Main Results:

  • N6L treatment decreased regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) while increasing activated tumor-infiltrated T lymphocytes (TILs).
  • NCL inhibition reduced cancer-associated fibroblast (CAF) expansion and decreased IL-6 levels in tumors and serum.
  • IL-6 blockade mimicked N6L's effects on immune cell populations.

Conclusions:

  • NCL inhibition effectively modulates the PDAC immune microenvironment by reducing immunosuppressive cells and promoting T cell activation.
  • The mechanism involves direct inhibition of the tumoral stroma and reduction of IL-6 signaling.
  • NCL inhibition represents a promising therapeutic strategy for PDAC by targeting tumor immunity and stromal components.
Keywords:
PDACimmune cellsnucleolinvessels

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