Endogenous IL-17 contributes to reduced tumor growth and metastasis - PubMed (original) (raw)

Endogenous IL-17 contributes to reduced tumor growth and metastasis

Ilona Kryczek et al. Blood. 2009.

Abstract

It has been reported that ectopically expressed interleukin-17 (IL-17) in tumor cells suppresses tumor progression through enhanced antitumor immunity in immune competent mice or promote tumor progression through an increase in inflammatory angiogenesis in immune-deficient mice. The role of endogenous IL-17 in tumor immunity remains undefined. Here we showed that tumor growth and lung metastasis were enhanced in IL-17-deficient mice, associated with decreased interferon-gamma(+) natural killer cells and tumor specific interferon-gamma(+) T cells in the tumor draining lymph nodes and tumors. Together with the published data showing that in vitro transforming growth factor-beta and IL-6-polarized Th17 cells induce tumor regression, our work supports the notion that endogenous IL-17 or/and Th17 cells may play a protective role in tumor immunity.

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Figures

Figure 1

Figure 1

Enhanced tumor growth and metastasis in IL-17–deficient mice. MC38 cells were inoculated into IL-17–deficient mice and normal wild-type mice as we described. (A) Enhanced tumor growth in IL-17–deficient mice. After tumor inoculation, tumor volume was measured as described in “Methods.” Results are expressed as mean ± SEM; n = 5 per group. (B) Enhanced tumor lung metastasis in IL-17–deficient mice. Thirty days after tumor inoculation, tumor colonies in the lungs were photographed and quantified; n = 6 per group.

Figure 2

Figure 2

Immune cells in the tumor and draining lymph nodes in IL-17–deficient mice. MC38 cells were inoculated into IL-17–deficient mice and normal wild-type mice as we described. Twenty-five days after tumor inoculation, single-cell (s.c.) suspensions were made from tumor tissues, tumor-draining lymph nodes (TDLN) and spleens, or non–tumor-bearing IL-17–deficient mice and wild-type mice. (A-E) Phenotype and cytokine profile of each immune cell subsets were analyzed by fluorescence-activated cell sorter. Results are the percentage of the targeted cell subset in a particular immune cell population. One representative of 5 experiments is shown in panels A to E (n = 13 mice per group in panels A-E). (A) T-cell subsets in tumor. Single-cell suspensions were made from tumor tissues. The levels of CD4+ and CD8+ T cells, and FOXP3+ T cells were quantified with LSR II by gating on CD3+ cells. The levels of these 3 T-cell subsets were comparable in IL-17–deficient mice and wild-type mice (P > .05 for all). (B) IL-10+ T cells and Treg cells in tumor. Single-cell suspensions were made from tumor tissues. The levels of IL-10+CD4+ T cells and CD4+FOXP3+ T cells were quantified with LSR II by gating on CD3+CD4+ cells. The levels of these 2 T-cell subsets were comparable in IL-17–deficient mice and wild-type mice (P > .05 for all). (C) IFN-γ+ T cells in tumor. Single-cell suspensions were made from tumor tissues. The levels of IFN-γ+CD4+ T cells and IFN-γ+CD8+ T cells were quantified with LSR II by gating on CD3+ cells. The levels of these 2 T-cell subsets were significantly lower in IL-17–deficient mice than wild-type mice (P < .01 for all). (D) NK cells in TDLNs. Single-cell suspensions were made from TDLNs. The levels of CD49b+NK1.1+ NK cells were quantified with LSR II by gating on CD3− cells. The levels of NK cells were significant lower in IL-17–deficient mice than wild-type mice (P < .01). (E) IFN-γ+ cells in TDLNs. Single-cell suspensions were made from TDLNs. The levels of IFN-γ+ NK cells, IFN-γ+CD4+ T cells, and IFN-γ+CD8+ T cells were quantified with LSR II by gating on NK cells and CD4+ and CD8+ T cells. The levels of these 3 IFN-γ+ cell subsets were significantly lower in IL-17–deficient mice than wild-type mice (P < .01 for all). (F) NK- and T-cell activities in tumor-bearing mice (top panels) and non–tumor-bearing mice (bottom panels). TDLN T cells were stimulated with irradiated MC38, and non–TDLN T cells were stimulated with phorbol-12-myristate-13-acetate and ionomycin. Spleen NK cells were stimulated with IL-2 and irradiated YAC-1 cells. The expression of IFN-γ was detected by ELISPOT assay in these stimulated T and NK cells. Results are mean ± SEM values of IFN-γ+ spots in triplicate wells. □ represent wild-type mice; and ■, IL-17–deficient mice. n = 5 mice per group. *P < .01. **P < .05.

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