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Therapeutic effectiveness of intratumorally delivered dendritic cells engineered to express the pro-inflammatory cytokine, interleukin (IL)-32.

ABSTRACT: Interleukin-32 (IL-32) is a pro-inflammatory cytokine conditionally produced by T cells, natural killer (NK) cells, monocytes, epithelial cells and keratinocytes, which has an important role in host resistance against infectious disease. Interestingly, elevated levels of IL-32 transcripts in fine needle aspirates of tumor tissue have also been correlated with objective clinical responses in cancer patients receiving immunotherapy. To evaluate the antitumor impact of IL-32 gene therapy, we treated BALB/c mice bearing established subcutaneous CMS4 sarcomas with intratumoral (i.t.) injections of syngenic dendritic cells (DCs) engineered to express human IL-32? complementary DNA (that is, DC.IL32). Although ectopic expression of IL-32? by DC resulted in only modest phenotypic changes in these antigen-presenting cells, DC.IL32 produced higher levels of IL-12p70 than control DC. DC.IL32 were more potent activators of type-1 T-cell responses in vitro and in vivo, with i.t. administration of DC.IL32 leading to the CD8(+) T-cell-dependent (but CD4(+) T-cell- and NK cell-independent) suppression of tumor growth. Effective DC.IL32-based therapy promoted infiltration of tumors by type-1 (that is, CXCR3(+)VLA-4(+)GrB(+)) CD8(+) T cells and CD11b(+)CD11c(+) host myeloid DC, but led to reductions in the prevalence of CD11b(+)Gr1(+) myeloid-derived suppressor cells and CD31(+) blood vessels.

SUBMITTER: Qu Y

PROVIDER: S-EPMC3348582 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Therapeutic effectiveness of intratumorally delivered dendritic cells engineered to express the pro-inflammatory cytokine, interleukin (IL)-32.

Qu Y Y Taylor J L JL Bose A A Storkus W J WJ

Cancer gene therapy 20110715 9

Interleukin-32 (IL-32) is a pro-inflammatory cytokine conditionally produced by T cells, natural killer (NK) cells, monocytes, epithelial cells and keratinocytes, which has an important role in host resistance against infectious disease. Interestingly, elevated levels of IL-32 transcripts in fine needle aspirates of tumor tissue have also been correlated with objective clinical responses in cancer patients receiving immunotherapy. To evaluate the antitumor impact of IL-32 gene therapy, we treate ...[more]

PMID: 21760628

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Project description:Mycetoma is a neglected tropical disease, endemic in many tropical and subtropical regions, characterised by massive deformity and disability and can be fatal if untreated early and appropriately. Interleukins (IL) -35 and IL-37 are newly discovered cytokines that play an important role in suppressing the immune system. However, the expression of these interleukins in patients with Madurella mycetomatis (M. mycetomatis) induced eumycetoma has not yet been explored. The aim of this study is to determine the levels of IL-1 family (IL-1β, IL-37) and IL-12 family (IL-12, IL-35) in a group of these patients and the association between these cytokines levels and the patients' demographic characteristics. The present, case-control study was conducted at the Mycetoma Research Centre, Soba University Hospital, University of Khartoum, Sudan and it included 140 individuals. They were divided into two groups; group I: healthy controls [n = 70; median age 25 years (range 12 to 70 years)]. Group II: mycetoma patients [n = 70 patients; median age 25 (range 13 to 70 years)]. Cytokines levels were measured in sera using enzyme linked immunosorbent assay (ELISA). There was a significant negative correlation between IL-1β and IL-12 levels and lesion size and disease duration, while IL-37 and IL-35 levels were significantly positively correlated with both lesion size and disease duration. The analysis of the risk factors of higher circulatory levels of IL-37 in patients of mycetoma showed a negative significant association with IL-1β cytokine, where a unit increment in IL-1β will decrease the levels of IL-37 by 35.28 pg/ml. The levels of IL-37 among the patients with a duration of mycetoma infection ≤ 1 year were significantly low by an average of 18.45 pg/ml compared to patients with a mycetoma infection's duration of ≥ 5years (reference group). Furthermore, the risk factors of higher levels of IL-35 in mycetoma patients revealed a negative significant association with IL-12, as a unit increment in IL-12 decreases the levels of IL-35 by 8.99 pg/ml (p < 0.001). Levels of IL-35 among the patients with duration of mycetoma infection ≤ one year were significantly low on average by 41.82 pg/ml (p value = 0.002) compared to patients with a duration of mycetoma infection ≥ 5 years (reference group). In conclusion, this study indicates that both IL-35 and IL-37 are negatively associated with the levels of IL-1β and IL-12 in eumycetoma mycetoma infection; and high levels of IL-37 and IL-35 may have a negative impact on disease progression.

Dataset Information

Therapeutic effectiveness of intratumorally delivered dendritic cells engineered to express the pro-inflammatory cytokine, interleukin (IL)-32.

Publications

Therapeutic effectiveness of intratumorally delivered dendritic cells engineered to express the pro-inflammatory cytokine, interleukin (IL)-32.

Similar Datasets

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