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CD40 Ligand--an anti-apoptotic molecule in Hodgkin's disease

S S Metkar1, P P Manna, M Anand

  • 1Immunology Division, Cancer Research Institute, Tata Memorial Centre, Parel, Mumbai 400 012, India.

Cancer Biotherapy & Radiopharmaceuticals
|March 31, 2001
PubMed

Insights

CD40 Ligand (CD40L) is upregulated in Hodgkin's disease (HD) and promotes cancer cell survival by increasing the anti-apoptotic gene BclxL, suggesting CD40L as a therapeutic target.

Area of Science:

  • Immunology
  • Molecular Biology
  • Oncology

Background:

  • Hodgkin's disease (HD) is a lymphoid malignancy characterized by the presence of Reed-Sternberg cells within the tumor microenvironment.
  • The role of immune cells and their signaling molecules in HD pathogenesis is not fully understood.
  • CD40 Ligand (CD40L) is a key molecule in immune cell interactions and survival signaling.

Purpose of the Study:

  • To investigate the expression of CD40L in lymph nodes of HD patients.
  • To determine the role of CD40L in the upregulation of the anti-apoptotic gene BclxL in an HD-derived cell line.

Main Methods:

  • Flow cytometry (FCM) and reverse transcriptase polymerase chain reaction (RT-PCR) were used to analyze CD40L expression.
  • HD patients (n=18) and controls (n=8) were compared for T cell activation and CD40L co-expression.
  • An HD cell line (HDLM2) was used to study the effect of soluble CD40L on BclxL expression.

Main Results:

  • HD patients showed significantly higher numbers of activated CD4+ and CD8+ T cells in the tumor microenvironment compared to controls.
  • Lymphocytes (CD4+, CD8+, CD19+) co-expressing CD40L were significantly increased in HD patients.
  • CD40L mRNA levels were consistently upregulated in HD patients (n=5) versus controls (n=3).
  • Soluble CD40L upregulated BclxL levels in the Fas-sensitive HDLM2 cell line.

Conclusions:

  • CD40 Ligand is upregulated in the tumor microenvironment of Hodgkin's disease.
  • CD40L acts as an anti-apoptotic molecule by upregulating BclxL expression in Reed-Sternberg cells.
  • CD40L may contribute to the survival of HD cells in vivo, presenting a potential therapeutic target.

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