Role of tumor‐derived proinflammatory cytokines GM‐CSF, TNF‐α, and IL‐12 in the migration and differentiation of antigen‐presenting cells in cervical carcinoma

Abstract

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‐α, 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‐α, 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‐α correlated positively with the number of TAM and DC. TNF‐α 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‐α, 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‐α, produced by cervical carcinoma cells, may play a role in the differentiation of monocytes into mature DC. Furthermore, TNF‐α may influence the migration of LHC from the tumor. Cancer 2007;109:556–565. © 2007 American Cancer Society.

Pretreatment plasma levels and diagnostic utility of hematopoietic cytokines in cervical cancer or cervical intraepithelial neoplasia patients

“…The inflammatory process and granulocytosis may be an explanation for the higher levels of G-CSF both in benign and malignant lesions of the cervix [13]. The investigations of Zijlmans et al [33] and Czygier et al [34] are in agreement with our data, and support the hypothesis that GM-CSF (among other cytokines) induces an inflammatory response which assists in tumor growth and progression.…”

Breast Cancer Cell–Derived GM-CSF Licenses Regulatory Th2 Induction by Plasmacytoid Predendritic Cells in Aggressive Disease Subtypes

“…Previous studies have shown the presence of GM-CSF in diverse type of tumors, including breast cancer (17,(44)(45)(46)(47). GM-CSF can function as an immune adjuvant by activating NK cells and myeloid cells (48), and is widely used in antitumor therapy (49,50).…”

Versican expression is associated with tumor-infiltrating CD8-positive T cells and infiltration depth in cervical cancer

“…CD68-positive cells, CD1a (Langerhans cells)-positive intraepithelial cells or DC-LAMPpositive stromal dendritic cells were visualized as described previously. 27 …”