Production by Human Squamous Cell Carcinoma of a Factor Inducing Activation and Proliferation of Immune Cells

Hirabayashi, Hideki; Yasumura, Satoshi; Lin, Wen-Chiao; Amoscato, Andrew A.; Johnson, Jonas T.; Herberman, Ronald B.; Whiteside, Theresa L.

doi:10.1001/archotol.1995.01890030025005

Cited by 9 publications

(5 citation statements)

References 21 publications

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“…PCI-51, a human head and neck squamous cell carcinoma (SCC) cell line, was established in our laboratory as previously described (Hirabayashi et al, 1995). K562, a human NK-sensitive cell line, derived from a patient with chronic myelogenous leukaemia, was maintained as described (Vujanovic et al, 1995a).…”

Section: Cell Lines and Reagentsmentioning

confidence: 99%

Inhibition of apoptosis in human tumour cells by the tumour-associated serpin, SCC antigen-1

et al. 2000

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SummaryThe squamous cell carcinoma antigen (SCC Ag) is a tumour-associated protein and a member of the serine protease inhibitor (serpin) family. The SCC Ag has been used as a serologic tumour marker for SCC progression, and its elevated serum levels are a risk factor for disease relapse. However, the biologic significance of this intracytoplasmic protein in cancer cells remains unknown. In this report, we demonstrated that apoptosis induced by 7-ethyl-10-hydroxycamptothecin, tumour necrosis factor-α (TNF-α) or interleukin (IL)-2-activated natural killer (NK) cells was significantly inhibited in tumour cells transduced with the SCC Ag-1 cDNA, as compared to control cells in vitro. Also, inhibition of the SCC Ag-1 expression in tumour cells by transfection of antisense SCC Ag-1 cDNA was accompanied by significantly increased sensitivity of these cells to apoptosis induced by etoposide or TNF-α. The mechanism of protection of tumour cells from apoptosis involved inhibition of caspase-3 activity and/or upstream proteases. In vivo, tumour cells overexpressing the SCC Ag-1 formed significantly larger tumours in nude mice than the SCC Ag-1-negative controls. Thus, overexpression of the SCC Ag-1, a member of the serpin family, in human cancer cells contributed to their survival by mediating protection from drug-, cytokine-or effector cell-induced apoptosis.

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Section: Cell Lines and Reagentsmentioning

confidence: 99%

Inhibition of apoptosis in human tumour cells by the tumour-associated serpin, SCC antigen-1

et al. 2000

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“…In addition, the T helper 1 (Th1) type cytokines cooperate with antigen-presenting cells in the induction of cytotoxic lymphocytes and upregulate the cytotoxic activity of TIL [11, 12]. TIL as well as cancer cells generate both Th1 type and T helper 2 (Th2) type cytokines, and the generated cytokines build an in situ cytokine network, influencing TIL and cancer cells and each other [13, 14, 15, 16, 17, 18]. However, the levels of cytokines generated by TIL and cancer cells have been infrequently examined, and the influence of cancer therapy on cytokine generation by TIL and cancer cells has not been well explored.…”

Section: Introductionmentioning

confidence: 99%

Characteristic Cytokine Generation Patterns in Cancer Cells and Infiltrating Lymphocytes in Oral Squamous Cell Carcinomas and the Influence of Chemoradiation Combined with Immunotherapy on These Patterns

et al. 2003

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Objectives: Cytokines produced by tumor cells and tumor-infiltrating lymphocytes (TIL) appear to regulate tumor cell growth and the cytotoxic activity of TIL. The objectives of the present study were to investigate cytokine generation patterns in tumor cells and TIL and to examine the influence of cancer therapy on this cytokine production and the cytotoxic activity of TIL. Methods: We determined the levels of cytokines produced by tumor cells and TIL in vitro and measured the cytotoxic activity of TIL against Daudi cells in patients with oral squamous cell carcinoma (OSC) before and 1 week after the start of concomitant chemo-radio-immunotherapy. Results: Before the therapy, OSC cells generated higher levels of granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) than did oral keratinocytes isolated from the noninflamed gingivae of healthy individuals, but both kinds of cells generated similar levels of interleukin (IL)-1β and IL-6. Compared with peripheral blood mononuclear cells (PBMC) of the patients, TIL produced higher levels of IL-1β, IL-6, IL-10, TNF-α and TGF-β, whereas their production of IL-12 and interferon-γ (IFN-γ) was only slightly higher than that in PBMC. After 1 week of therapy, the cytokine production by OSC cells had largely decreased, while the production of TNF-α, IFN-γ, TGF-β and IL-12 by TIL had increased greatly, although other cytokine levels were almost constant during the investigations. The cytotoxic activity of TIL was higher than that of PBMC before the therapy, and this activity was strongly increased by 1 week of therapy. Conclusions: These results suggest that the cytokine productivities of TIL and tumor cells differ from those of PBMC and normal keratinocytes, respectively, and that chemo-radio-immunotherapy modulates in situ cytokine generation, which is advantageous for inhibition of tumor cell growth and activation of TIL.

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“…On one side, it was found that the lymphocytic secretion of some cytokines, in particular IL-2, was inhibited [6], while the secretion of other cytokines, i.e. IFN-Á, TNF-· and IL-6 by NK or T cells, were found to be enhanced by culture supernatants of different tumor cell lines [17]. On the other side, an insufficient production of IFN-Á by whole blood cultures from CRC and other tumor patients was also reported [3,4].…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Effects of Immunosuppressive Factors from Newly Established Colon Carcinoma Cell Cultures on Human Lymphocyte Proliferation and Cytokine Secretion

Luo

Kammerer²,

Kleist³

2000

Tumor Biol

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Tumor cells may influence the host’s immune reactivity by the production of immunosuppressive factors (ISFs). In this study, the effects of ISFs derived from nine polyclonal colorectal carcinoma (CRC) cell lines on PHA-induced lymphocyte proliferation and cytokine secretion was investigated. We found that most of the culture supernatants (8/9) from CRC cell lines contained ISFs, which inhibited T cell proliferation to a variable degree in a dose-dependent manner. Comparison of T cell proliferation in the presence or absence of monocytes showed that monocytes can modulate the effects of tumor-derived ISFs on lymphocyte function. In addition, exposure of activated PBMC to the tumor cell supernatants resulted in an altered secretion of cytokines by these cells, i.e. the secretion of IFN-γ was generally reduced while the secretion of IL-1β, IL-2 and TNF-α was little affected. We further investigated the supernatants’ inhibitory effects on PBMC in respect to the production of prostaglandin E₂ (PGE₂). It was found that PGE₂ was secreted by all tumor cell cultures. Therefore this substance is probably involved in the immunosuppression in vivo. However, the secreted PGE₂ was shown not to be solely responsible for the observed suppression of lymphocyte proliferation in vitro. Our results suggest that the secretion of ISF is a common property of CRCs as demonstrated with newly established CRC cell cultures, and therefore this may also be an important immune escape mechanism of colonic carcinomas in vivo.

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Production by Human Squamous Cell Carcinoma of a Factor Inducing Activation and Proliferation of Immune Cells

Cited by 9 publications

References 21 publications

Inhibition of apoptosis in human tumour cells by the tumour-associated serpin, SCC antigen-1

Inhibition of apoptosis in human tumour cells by the tumour-associated serpin, SCC antigen-1

Characteristic Cytokine Generation Patterns in Cancer Cells and Infiltrating Lymphocytes in Oral Squamous Cell Carcinomas and the Influence of Chemoradiation Combined with Immunotherapy on These Patterns

Comparison of the Effects of Immunosuppressive Factors from Newly Established Colon Carcinoma Cell Cultures on Human Lymphocyte Proliferation and Cytokine Secretion

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