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Antipancreatic cancer effect of DNT cells and the underlying mechanism

Jiong Chen1, Pibo Hu1, Gaohua Wu1

  • 1Department of General Surgery, Anhui Provincial Hospital Affiliated to Anhui Medical University, 17 Lujiang Road, Hefei, 230001, Anhui Province, PR China; Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Hefei, 230001, PR China.

Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [Et Al.]
|December 24, 2018
PubMed
Abstract

Insights

Double-negative T (DNT) cells show potent cytotoxicity against pancreatic cancer by inducing apoptosis. The Fas/FasL pathway is crucial for DNT cell-mediated inhibition of pancreatic cancer growth.

Area of Science:

  • Immunology
  • Oncology
  • Cell Biology

Background:

  • Pancreatic cancer remains a significant health challenge with limited effective therapies.
  • Double-negative T (DNT) cells represent a unique lymphocyte subset with potential immunomodulatory functions.

Purpose of the Study:

  • To investigate the cytotoxic effects of DNT cells on pancreatic cancer.
  • To elucidate the role of the Fas/FasL signaling pathway in DNT cell-mediated pancreatic cancer suppression.

Main Methods:

  • In vitro expansion of DNT cells from healthy volunteer peripheral blood.
  • Assessment of DNT cell cytotoxicity using CCK-8 assays and a nude mouse tumor model.
  • Mechanistic investigation via pathway blocking assays, including the use of decoy receptor 3 (DcR3).

Main Results:

  • DNT cells significantly inhibited pancreatic cancer cell growth in vitro and reduced tumor volume and weight in vivo.
  • DNT cell treatment increased the expression of Fas, caspase-8, and cleaved caspase-8 in pancreatic cancer cells.
  • Blocking the Fas/FasL pathway with DcR3 diminished the antitumor effects of DNT cells and reduced apoptosis induction.

Conclusions:

  • DNT cells demonstrate significant antitumor activity against pancreatic cancer.
  • The Fas/FasL signaling pathway plays a critical role in mediating the cytotoxic effects of DNT cells on pancreatic cancer.
Keywords:
DNT cellFasFasLPancreatic cancer

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