Cytokine production of lung cancer cell lines: Correlation between their production and the inflammatory/immunological responses both in vivo and in vitro

Abstract

Cytokines produced by tumor cells may have various effects on antitumor immune responses and tumor growth. In the present study, the cytokine production of 31 lung cancer cell lines was evaluated, while any correlation with the histological type, the induction of tumor‐specific cytotoxic T lymphocytes (CTL) in vitro, and angiogenesis and the infiltration of inflammatory cells in tumor tissues were also examined. Production of interleukin (IL)‐1α, IL‐1β, IL‐4, IL‐6, IL‐8, IL‐10, tumor necrosis factor (TNF)‐α, granulocyte macrophage colony stimulating factor (GM‐CSF), granulocyte colony stimulating factor, transforming growth factor (TGF)‐β and vascular endothelial growth factor (VEGF) in the culture supernatant was measured using enzyme‐linked immunosorbent assay. Each cytokine was produced in a substantial number of the tumor cell lines. In particular, IL‐6, IL‐8, TGF‐β and VEGF were produced in 18 (55%), 29 (94%), 31 (100%) and 28 (90%) of 31 cell lines, respectively. However, neither IL‐4 nor TNF‐α was produced at all by any tumor cell line. TGF‐β production was significantly higher in adenocarcinoma than in squamous cell carcinoma (P = 0.03). Immunohistochemical staining revealed the magnitude of macrophage infiltration, and angiogenesis in surgically resected tumor tissue specimens correlated well with GM‐CSF and IL‐8 production from the corresponding cell lines. Among six lung cancer cell lines, CTL were induced in the three lung cancer cell lines that produced a lower amount of TGF‐β (<100 pg/mL). These findings suggested that TGF‐β produced by tumor cells could inhibit the induction of CTL in vitro. The present results suggest that the production of various cytokines from tumor cells might exert various paracrine effects both in vivo and in vitro. (Cancer Sci 2007; 98: 1048–1054)

Immunosuppressive effect of regulatory T lymphocytes in lung cancer, with special reference to their effects on the induction of autologous tumor-specific cytotoxic T lymphocytes

“…We have previously reported that TGF-β production varied among lung cancer cell lines, and that the induction of CTLs tended to fail against tumor cell lines with a high level of TGF-β production (18). In that study, as a higher production of TGF-β in the tumor cells was noted, a lower induction of CTLs was observed.…”

“…In both of the groups with added TGF-β, the induction of CTLs was inhibited. However, in the group cultured without TGF-β, CTL induction was achieved in 2 out of 3 wells, as described previously (18). In the same experiment, we analyzed the proportion of Tregs 28 days after MLTC, and the proportion of CD4 + CD25 + Foxp3 + Tregs in each sample was analyzed using a FACSCalibur instrument.…”

“…During the MLTC, various amounts of TGF-β (0, 100 or 400 pg/ml) were added every day as described previously (18). In both of the groups with added TGF-β, the induction of CTLs was inhibited.…”

Multiple Cytokines-Producing Pleomorphic Carcinoma of Lung with Metastasis to the Small Intestine

“…3,4) These cytokines are thought to have various effects on tumor growth and antitumor immune responses. G-CSF is a member of the CSF family of glycoproteins that control the survival, proliferation, differentiation, and functional activation of hematopoietic progenitor cells.…”

“…1) Pleomorphic carcinoma of the lung is rare and accounts for less than 1% of all lung malignancies. 2) Although there have been several reports that some types of lung cancers produce various cytokines such as granulocyte colony-stimulating factor (G-CSF), interleukin 6 (IL-6), and IL-8, 3) there have been few reports of pleomorphic carcinoma of the lung producing these cytokines. We describe a rare case of G-CSF and tumor necrosis factor (TNF)-a producing pleomorphic carcinoma of the lung.…”