Table 1: Examples of antitumor and protumor effects of IL-27 in different models.
(a) Antitumor effects

Target cells or modelsMajor effectsRef.

Direct antitumor effects
AML cells implanted in NOD/SCID/Il-2rγ−/− miceIL-27 suppressed human pediatric AML cell expansion, survival, and invasive properties[21]
NSCLC cells in xenotransplant modelsIL-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 miceIL-27 treatment reduced proliferation and vascularization in association with ischemic necrosis of tumors[23]
Human multiple myeloma xenotransplant modelsIL-27 treatment suppressed angiogenesis, osteoclast differentiation, and bone erosive activity, while it supported osteoblast proliferation[24]
Human ovarian cancer, neuroblastomaIL-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 lineThe overexpression of IL-27 enhanced cell death and inhibited the proliferation of SKOV3 cells[26]
Human NSCLC cellsThe combined use of the COX-2 inhibitor Apricoxib and IL-27 cooperatively inhibited EMT transition[27]
Human NSCLC cellsIL-27 suppressed epithelial-mesenchymal transition and expression of proangiogenic factors[28]
Mouse melanoma B16F10 cell transfectants expressing wild-type WSX1IL-27 showed antiproliferative activity on melanomas through WSX1/STAT1 signaling[29]
Human melanoma in immunodeficient miceCombination of IL-27 with the TLR3 ligand poly (I:C) cooperatively suppressed melanoma growth[30]

Indirect antitumor effects by targeting the tumor microenvironment
B16F10 mouse melanoma modelIL-27 induced production of antiangiogenic chemokines CXCL9 and CXCL10 by endothelial cells[31]
Primary endothelial cellsIL-27 induced CXCL9 and CXCL10 gene expression[32]
C26 colon carcinoma cells transduced with the single-chain IL-27 cDNAIL-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-27TBJ-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 miceIL-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 miceTumor growth was retarded in vivo, possibly through enhanced NK cell activity and IFN-γ production[37]
Human promonocytic cell line U937IL-27 inhibited the M2 macrophage polarization[38]
IL27RA(−/−) mice bred with mutant p53 heterozygous (p53(R172H/+)) miceMore 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, respectivelyReduced 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]

Only selected references are reported.
(b) Protumor effects

Target cells or modelsMajor findingsRef.

OCI-AML5 acute myeloid leukemia and TF-1, UT-7, and UT-7/EPO erythroleukemic cell linesIL-27 promoted survival, reduced TNF-α-induced apoptosis, and decreased the responsiveness of adult AML cells to cytarabine and daunorubicin[41]
Human ovarian cancer cellsIL-27 induced the expression of immune-regulatory molecules such as IL-18BP, PD-L1, and IDO in human ovarian cancer cells[42, 43]
Human ovarian cancer-associated macrophagesIL-27 induced CD39 expression and acquisition of immune-regulatory activity[44]
Human lymphoma macrophagesIL-27 induced PD-L1/2 expression through a STAT3-dependent mechanism[45]
Mouse tumor-associated T lymphocytesIL-27 induced the expression of Tim-3, a potent inducer of the T cell dysfunction, and IL-10[46]