Related Experiment Video

Updated: May 28, 2026

Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
09:15

Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine

Published on: February 24, 2023

IL-2 regulates the expression of the tumor suppressor IL-24 in melanoma cells

Emily Y Jen1, Nancy J Poindexter, Elizabeth S Farnsworth

  • 1Department of Experimental Therapeutics, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.

Melanoma Research
|October 27, 2011
PubMed

Insights

Interleukin-2 (IL-2) therapy can suppress melanoma growth by directly increasing the tumor suppressor Interleukin-24 (IL-24) in a subset of melanoma cells. This mechanism explains some clinical benefits of IL-2 treatment for metastatic melanoma.

Area of Science:

  • Oncology
  • Immunotherapy
  • Molecular Biology

Background:

  • Melanoma exhibits resistance to chemotherapy.
  • Biotherapies like Interleukin-2 (IL-2) show variable responses in metastatic melanoma patients.
  • Systemic IL-2 offers clinical benefit and long-term survival in a subset of patients.

Purpose of the Study:

  • To investigate the hypothesis that IL-2 therapy upregulates the tumor suppressor IL-24 in melanoma cells.
  • To identify a novel mechanism for IL-2's therapeutic efficacy in melanoma.

Main Methods:

  • Treatment of five melanoma cell lines with high-dose recombinant human IL-2.
  • Assessment of IL-24 protein and mRNA expression.
  • Blocking IL-2 signaling with antibodies against IL-2 and its receptor chains (IL-2Rβ, IL-2Rγ).
  • Analysis of signal transducer and activator of transcription (STAT) activation.
  • Evaluation of cell growth suppression and reversal using anti-IL-24 antibodies and IL-24 small interfering RNA.

Main Results:

  • Three out of five melanoma cell lines (A375, WM1341, WM793) showed significant increases in IL-24 protein and mRNA upon IL-2 treatment.
  • IL-2-induced IL-24 upregulation was dependent on functional IL-2 receptor beta and gamma chains.
  • IL-24 upregulation and subsequent melanoma cell growth suppression were observed in response to both IL-2 and IL-15.
  • Reversal of IL-2-mediated growth suppression was achieved by blocking IL-24.

Conclusions:

  • Direct upregulation of the tumor suppressor IL-24 by IL-2 is a mechanism contributing to effective IL-2 therapy in a subset of melanoma patients.
  • IL-2 responsiveness and IL-24 induction are linked to the expression of IL-2 receptor beta and gamma chains.
  • This study identifies a distinct subset of melanoma cells sensitive to IL-2 via IL-24 induction, offering potential therapeutic targets.

More Related Videos

Visualization of IL-22-expressing Lymphocytes Using Reporter Mice10:30

Visualization of IL-22-expressing Lymphocytes Using Reporter Mice

Published on: January 25, 2017

Generation of Induced Pluripotent Stem Cells from Human Melanoma Tumor-infiltrating Lymphocytes10:03

Generation of Induced Pluripotent Stem Cells from Human Melanoma Tumor-infiltrating Lymphocytes

Published on: November 11, 2016

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
Tumor Immunotherapy01:27

Tumor Immunotherapy

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.
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...