Related Experiment Video

Updated: Jul 8, 2026

Real Time Detection of In Vitro Tumor Cell Apoptosis Induced by CD8+ T Cells to Study Immune Suppressive Functions of Tumor-infiltrating Myeloid Cells
09:57

Real Time Detection of In Vitro Tumor Cell Apoptosis Induced by CD8+ T Cells to Study Immune Suppressive Functions of Tumor-infiltrating Myeloid Cells

Published on: January 29, 2019

Apoptosis resistance in epithelial tumors is mediated by tumor-cell-derived interleukin-4

M Todaro1, Y Lombardo, M G Francipane

  • 1Department of Surgical and Oncological Sciences, University of Palermo, Palermo, Italy.

Cell Death and Differentiation
|January 19, 2008
PubMed

Insights

Epithelial cancers resist cell death by producing interleukin-4 (IL-4), which boosts anti-apoptotic proteins. Blocking IL-4 reduces cancer growth and increases sensitivity to treatments by lowering these proteins.

Area of Science:

  • Oncology
  • Cell Biology
  • Immunology

Background:

  • Epithelial cancers exhibit resistance to cell death.
  • Key anti-apoptotic proteins like PED, cFLIP, Bcl-xL, and Bcl-2 are implicated in this resistance.

Purpose of the Study:

  • To investigate the role of interleukin-4 (IL-4) in mediating resistance to cell death in epithelial cancers.
  • To explore the potential of targeting IL-4 signaling as a therapeutic strategy.

Main Methods:

  • Analysis of anti-apoptotic protein expression in primary colon, breast, and lung carcinoma cells.
  • Assessment of IL-4 production and its effect on cell death pathways.
  • Evaluation of IL-4 blockade's impact on cancer cell growth and apoptosis induction in vitro and in vivo.

Main Results:

  • Epithelial cancer cells express high levels of PED, cFLIP, Bcl-xL, and Bcl-2.
  • IL-4 amplifies these anti-apoptotic proteins, preventing TRAIL- or drug-induced cell death.
  • IL-4 blockade significantly decreases cancer cell growth and sensitizes cells to apoptosis by downregulating these proteins.
  • Exogenous IL-4 promotes apoptosis resistance in normal epithelial cells.

Conclusions:

  • IL-4 functions as an autocrine survival factor in epithelial cells.
  • Inhibition of IL-4/IL-4R signaling represents a potential novel therapeutic approach for epithelial cancers.

More Related Videos

Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice07:36

Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice

Published on: June 12, 2021

Related Concept Videos

The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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.
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.
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...