Related Experiment Video
Updated: Jul 18, 2026

In Vitro Differentiation of Mouse Granulocyte-macrophage-colony-stimulating Factor (GM-CSF)-producing T Helper (THGM) Cells
Published on: September 10, 2018
Role of tumor-derived proinflammatory cytokines GM-CSF, TNF-alpha, and IL-12 in the migration and differentiation of
Henry J M A A Zijlmans1, Gert Jan Fleuren, Hans J Baelde
1Department of Pathology, Leiden University Medical Center, Leiden, Netherlands.
Background:
Proinflammatory cytokines are important in modifying the activity, differentiation, and migration of antigen-presenting cells and may influence the survival of cancer patients. The study assessed whether GM-CSF, TNF-alpha, and IL-12, produced by cervical cancer cells, are important for the activity, differentiation, and migration of antigen-presenting cells.
Methods:
In 90 patients with cervical carcinoma the number of monocytes/tumor-associated macrophages (TAM), mature dendritic cells (DC), and Langerhans cells (LHC) was determined using immunohistochemistry. An RNA in situ hybridization technique was used to measure the expression level of GM-CSF, TNF-alpha, IL-12p35, and IL-12p40.
Results:
TAM were detected intraepithelial as well as in the stroma of the tumor. LHC were only detected intraepithelial and mature DC only in the tumor stroma. The number of TAM correlated positively with the number of mature DC. The expression levels of GM-CSF and TNF-alpha correlated positively with the number of TAM and DC. TNF-alpha showed a negative correlation with the number of LHC. A significant correlation between the expression of functional IL-12 (IL-12p40) and stromal TAM was found. The expression of GM-CSF, TNF-alpha, and IL-12p40 did not correlate significantly with disease-free survival. However, high IL-12p40 expression was associated with a favorable cumulative overall survival.
Conclusions:
The results suggest that GM-CSF as well as TNF-alpha, produced by cervical carcinoma cells, may play a role in the differentiation of monocytes into mature DC. Furthermore, TNF-alpha may influence the migration of LHC from the tumor.
Related Concept Videos
T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Differentiation of Common Myeloid Progenitor Cells
The Tumor Microenvironment
T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...
Regulation of Hematopoietic Stem Cells
Tumor Immunotherapy