(a) Antitumor effects
| Target cells or models | Major effects | Ref.a |
|---|---|---|
| Direct antitumor effects | ||
| AML cells implanted in NOD/SCID/Il-2rγ−/− mice | IL-27 suppressed human pediatric AML cell expansion, survival, and invasive properties | [21] |
| NSCLC cells in xenotransplant models | IL-27 downregulated stemness and EMT genes in human NSCLC cells and activates intratumor myeloid cells to exert antitumor effects | [22] |
| PC3 or DU145 human prostate cancer cell injection in athymic nude mice | IL-27 treatment reduced proliferation and vascularization in association with ischemic necrosis of tumors | [23] |
| Human multiple myeloma xenotransplant models | IL-27 treatment suppressed angiogenesis, osteoclast differentiation, and bone erosive activity, while it supported osteoblast proliferation | [24] |
| Human ovarian cancer, neuroblastoma | IL-27 induced HLA class-I antigen presentation machinery component expression and surface HLA class-I molecules and inhibited survival and migration of ovarian cancer cells | [25] |
| SKOV3 human ovarian cancer cell line | The overexpression of IL-27 enhanced cell death and inhibited the proliferation of SKOV3 cells | [26] |
| Human NSCLC cells | The combined use of the COX-2 inhibitor Apricoxib and IL-27 cooperatively inhibited EMT transition | [27] |
| Human NSCLC cells | IL-27 suppressed epithelial-mesenchymal transition and expression of proangiogenic factors | [28] |
| Mouse melanoma B16F10 cell transfectants expressing wild-type WSX1 | IL-27 showed antiproliferative activity on melanomas through WSX1/STAT1 signaling | [29] |
| Human melanoma in immunodeficient mice | Combination of IL-27 with the TLR3 ligand poly (I:C) cooperatively suppressed melanoma growth | [30] |
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| Indirect antitumor effects by targeting the tumor microenvironment | ||
| B16F10 mouse melanoma model | IL-27 induced production of antiangiogenic chemokines CXCL9 and CXCL10 by endothelial cells | [31] |
| Primary endothelial cells | IL-27 induced CXCL9 and CXCL10 gene expression | [32] |
| C26 colon carcinoma cells transduced with the single-chain IL-27 cDNA | IL-27-dependent tumor-specific activity and protective immunity are mediated mainly through CD8+ CTLs and production of IFN-γ | [33] |
| Mouse TBJ neuroblastoma cells engineered to overexpress IL-27 | TBJ-IL-27 tumors showed enhanced IFN-γ and MHC class-I expression in conjunction with tumor-specific CD8+ CTL reactivity. IL-27 and IL-2 cooperated in inducing regression of metastases | [34, 35] |
| Head and neck squamous cell carcinoma and IL-27 gene transfer in syngeneic mice | IL-27 induced T-bet and perforin in NK cells. It inhibited the growth of NK-resistant tumors through induction of NK-mediated ADCC | [36] |
| Eca109 human oesophageal carcinoma cells expressing IL-27 in nude mice | Tumor growth was retarded in vivo, possibly through enhanced NK cell activity and IFN-γ production | [37] |
| Human promonocytic cell line U937 | IL-27 inhibited the M2 macrophage polarization | [38] |
| IL27RA(−/−) mice bred with mutant p53 heterozygous (p53(R172H/+)) mice | More rapid spontaneous tumor development and reduced survival of IL27RA(−/−)p53(H/+ or H/H) mice relative to their WSX1(+/+) counterparts | [39] |
| J558 plasmacytoma or B16 melanoma injected in EBI3-deficient BALB/c or C57BL/6 mice, respectively | Reduced antitumor immune responses and enhanced tumor growth relative to wild-type control mice. Tumors from EBI3-deficient mice contained significantly decreased proportions of CD8+ T cells and increased proportions of CD4+FoxP3+ Treg cells | [40] |
aOnly selected references are reported.