Inoculation of Human Interleukin-17 Gene-Transfected Meth-A Fibrosarcoma Cells Induces T Cell-Dependent Tumor-Specific Immunity in Mice

Hirahara, Noriyuki; Nio, Yoshinori; Sasaki, Susumu; Minari, Yoshimitu; Takamura, Michio; Iguchi, Chikage; Dong, M. K.; Yamasawa, Kunihiro; Tamura, Katsuhiro

doi:10.1159/000055357

Cited by 111 publications

(83 citation statements)

References 26 publications

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“…However, the role of IL-17 and Th17 cells in antitumor immunity remains controversial. In some tumor models, expression of IL-17 can boost antitumor immunity by promoting the development of Ag-specific cytotoxic T cells (47,48). Tumorspecific Th17 cells have been shown to eradicate established and advanced B16 melanoma in an adoptive transfer therapeutic tumor model (49).…”

Section: Discussionmentioning

confidence: 99%

Tumor Microenvironments Direct the Recruitment and Expansion of Human Th17 Cells

Su¹,

Ye²,

Hsueh

et al. 2009

The Journal of Immunology

303

234

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Although Th17 cells play critical roles in the pathogenesis of many inflammatory and autoimmune diseases, their prevalence among tumor-infiltrating lymphocytes (TILs) and function in human tumor immunity remains largely unknown. We have recently demonstrated high percentages of Th17 cells in TILs from ovarian cancer patients, but the mechanisms of accumulation of these Th17 cells in the tumor microenvironment are still unclear. In this study, we further showed elevated Th17 cell populations in the TILs obtained from melanoma and breast and colon cancers, suggesting that development of tumor-infiltrating CD4+ Th17 cells may be a general feature in cancer patients. We then demonstrated that tumor microenvironmental RANTES and MCP-1 secreted by tumor cells and tumor-derived fibroblasts mediate the recruitment of Th17 cells. In addition to their recruitment, we found that tumor cells and tumor-derived fibroblasts produce a proinflammatory cytokine milieu as well as provide cell–cell contact engagement that facilitates the generation and expansion of Th17 cells. We also showed that inflammatory TLR and nucleotide oligomerization binding domain 2 signaling promote the attraction and generation of Th17 cells induced by tumor cells and tumor-derived fibroblasts. These results identify Th17 cells as an important component of human TILs, demonstrate mechanisms involved in the recruitment and regulation of Th17 cells in tumor microenvironments, and provide new insights relevant for the development of novel cancer immunotherapeutic approaches.

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Section: Discussionmentioning

confidence: 99%

Tumor Microenvironments Direct the Recruitment and Expansion of Human Th17 Cells

Su¹,

Ye²,

Hsueh

et al. 2009

The Journal of Immunology

303

234

View full text Add to dashboard Cite

show abstract

“…Forced overexpression of Il-17 ectopically in tumor cells can either suppress tumor progression through enhanced antitumor immunity (12,30) or promote it through an increase in inflammation and angiogenesis (11). the role of endogenous Il-17 in tumorigenesis has been assessed with Il-17 knockout mice (13).…”

Section: Discussionmentioning

confidence: 99%

Tumor-infiltrating CD4+ Th17 cells produce IL-17 in tumor microenvironment and promote tumor progression in human gastric cancer

Iida

Itō

Katsuda³

et al. 2011

Oncol Rep

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Abstract. recently, a subset of Il-17 producing t cells distinct from th1 or th2 cells has been described as key players in inflammation and autoimmune diseases as well as cancer development. In this study, we investigated the expression level of Il-17 and t helper 17 (th17)-related cytokines in gastric cancer tissues and assessed the association of their expression with angiogenesis and their clinicopathological parameters. tumor and adjacent normal tissues were obtained from 82 patients with gastric cancer. Il-17, Il-21 and Il-23 mRNA expression levels were quantified by real-time RT-PCR. Th17 infiltration, microvessel density and neutrophil infiltration in tumor tissues were examined by immunohistochemistry and double immunofluorescence histochemistry. Expression of IL-17, IL-21 and IL-23 mRNA was found to be significantly up-regulated in tumor tissues compared with adjacent normal tissues. the expression level of Il-17 mrnA strongly and positively correlated with that of Il-21 mrnA in tumor tissue. the number of vascular endothelial cells and infiltrating neutrophils was significantly larger in tumors expressing a high level of Il-17 mrnA than in tumors expressing a low level of Il-17 mrnA. In tumor tissues most cD4 + cells were stained with anti-Il-17 antibody. the expression level of Il-17 mrnA in gastric tumors was associated with the depth of the tumors, lymph-vascular invasion and lymph node involvement, suggesting that Il-17 obviously was related to tumor progression. Il-17 and Il-21, which regulates Il-17, would be potential therapeutic targets for the treatment of gastric cancer.

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“…In mice, the effect of IL-17 on in vivo tumor growth seems to depend largely on the tumor immunogenicity and cell types, as we and other groups have shown that IL-17 inhibits tumor growth in a T-cell-dependent manner. 24,46 In contrast, IL-17 has also been shown to promote tumor cell growth via proangiogenic and IL-6-dependent mechanisms. 12,35,47 In the present study, 5 out of 10 MF/SS biopsies expressed IL-17, but in this small series of patients, no clear-cut difference in the expression of this cytokine was observed in MF or SS patients.…”

Section: Discussionmentioning

confidence: 99%

Expression and activity of IL‐17 in cutaneous T‐cell lymphomas (mycosis fungoides and sezary syndrome)

Cirée

Michel

Camilleri-Broët

et al. 2004

Intl Journal of Cancer

103

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Interleukin-17 (IL-17) is a proinflammatory cytokine mainly produced by activated CD4 ؉ CD45RO T cells. In mice, we have demonstrated that, depending on the model, IL-17 may act as a tumor growth-promoting or -inhibiting factor. In order to address the relevance of these models in human tumors, we look for the natural expression and activity of IL-17 in mycosis fungoides (MF) and Sezary syndrome (SS). These cutaneous T-cell lymphomas were selected because they are usually CD3 ؉ CD4 ؉ CD45RO ؉ , a phenotype similar to nontransformed T cells producing IL-17. We show that in vitro activated malignant T cells derived from MF or SS patients express IL-17 mRNA and secrete this cytokine. However, IL-17 does not act in vitro as a growth factor for MF or SS cell lines. In addition, 5 out of 10 MF/SS biopsies expressed IL-17 mRNA, while this cytokine was not detected in normal skin. IL-17 was not observed in the biopsies derived from 2 patients initially identified as MF, whereas an upregulation of this cytokine was clearly demonstrated during progression of the disease in these patients. An association between IL-17 expression and polymorphonuclear neutrophil infiltration was also recorded in this group of MF/SS patients. A more detailed analysis of 2 patients with a pustular form of MF and SS revealed that IL-17 may participate in the recruitment of polymorphonuclear neutrophils via a paracrine mechanism involving keratinocyte-released IL-8. This study is the first report demonstrating that some human tumor cells could express IL-17, a cytokine that represents an early event in the development of the inflammatory reaction within the tumor microenvironment, a process that may influence tumor phenotype and growth.

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Inoculation of Human Interleukin-17 Gene-Transfected Meth-A Fibrosarcoma Cells Induces T Cell-Dependent Tumor-Specific Immunity in Mice

Cited by 111 publications

References 26 publications

Tumor Microenvironments Direct the Recruitment and Expansion of Human Th17 Cells

Tumor Microenvironments Direct the Recruitment and Expansion of Human Th17 Cells

Tumor-infiltrating CD4+ Th17 cells produce IL-17 in tumor microenvironment and promote tumor progression in human gastric cancer

Expression and activity of IL‐17 in cutaneous T‐cell lymphomas (mycosis fungoides and sezary syndrome)

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