Ifn-Gamma and B7 as Costimulators of Antitumor Immune-Responses

Flores, Iván; Sarkar, Saumendra N.; Derosa, Clorinda; Ozzello, Luciano; Nabavi, Noushin; Shen, Y. R.; Ron, Yacov; Pestka, S

doi:10.3892/ijo.7.3.501

Cited by 4 publications

(5 citation statements)

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“…IFN-γ-stimulated CTL and NK cell activity also results in a potent anti-tumor effect of IFN-γ-endostatin-based gene-radiotherapy in 4T1 tumor model 23 . Inhibition of B16 melanoma in mice by IFN-γ is synergized by IFN-α, while overexpressing interferon regulatory factor-2 results in resistance of B16 melanoma to endogenous IFN-γ 24 25 26 . Expression of IFN-γ by lung NK cells can resist the pulmonary metastasis.…”

Section: Discussionmentioning

confidence: 99%

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Activation of liver X receptor inhibits the development of pulmonary carcinomas induced by 3-methylcholanthrene and butylated hydroxytoluene in BALB/c mice

Wang

Sun

Yang

et al. 2016

Sci Rep

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We previously reported that LXR ligand, T0901317, inhibited the growth of inoculated Lewis lung carcinoma in C57BL/6 mice by activating IFN-γ production. However, the effects of T0901317 on carcinogen-induced pulmonary carcinomas remain unknown. In this study, we initially conducted a statistical analysis on the data of human lung cancer samples extracted from the TCGA database, and determined that survival rate/time of lung cancer patients and grade of lung adenocarcinoma were positively and negatively related to lung IFN-γ levels, respectively. We then determined the inhibitory effects of T0901317 on mouse pulmonary carcinomas induced by 3-methylcholanthrene (MCA) and butylated hydroxytoluene (BHT) or urethane. We found that T0901317 reduced morbidity and mortality in MCA/BHT-injected BALB/c mice by inhibiting lung adenocarcinoma. T0901317 also protected C57BL/6 mice, but not IFN-γ deficient (IFN-γ−/−, C57BL/6 background) mice, against MCA/BHT-induced lung hyperplasia/inflammation. In addition, we determined that T0901317 inhibited urethane-induced lung tumors in BABL/c mice. Furthermore, we determined that T0901317 prevented metastasis of 4T1 breast cancer cells in BALB/c mice. Administration of T0901317 substantially increased serum IFN-γ levels and lung IFN-γ expression in BABL/c and C57BL/6 mice. Taken together, our study demonstrates that LXR inhibits MCA/BHT-induced pulmonary carcinomas in BABL/c mice and the inhibition is associated with induction of IFN-γ production.

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Section: Discussionmentioning

confidence: 99%

“…Expression of IFN-γ by lung NK cells can resist the pulmonary metastasis. IFN-γ also functions as a co-stimulator with T cell costimulatory molecule B7 to activate the antitumor immune-response in mice 26 27 .…”

Section: Discussionmentioning

confidence: 99%

Activation of liver X receptor inhibits the development of pulmonary carcinomas induced by 3-methylcholanthrene and butylated hydroxytoluene in BALB/c mice

Wang

Sun

Yang

et al. 2016

Sci Rep

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“…25,26 In addition, separate studies have shown that transfected IFN-␣ plasmid DNA could produce an antiviral effect as well as antitumor activities both in vitro and in vivo. [27][28][29][30] Therefore, transient expression of IFNs can be used to determine their physical and biologic functions. Because purified IFN-had lower activity, we performed transient transfection studies to determine the antiviral potential of IFN-as compared with IFN-␣2b.…”

Section: Discussionmentioning

confidence: 99%

Antiviral Activity of Transiently Expressed IFN-κ Is Cell-Associated

Buontempo¹,

Jubin²,

Buontempo³

et al. 2006

Journal of Interferon & Cytokine Research

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Most type I interferons (IFNs) are expressed by the majority of cell types in response to viral infection. In contrast, IFN-kappa has been reported to have a cellular distribution limited to keratinocytes and certain lymphoid cell populations. Recombinant expressed IFN-kappa has been shown previously to possess weak antiviral activity when directly compared with IFN-beta. In order to expand on the antiviral potential of IFN-kappa, we transiently transfected human cell lines to circumvent the need to purify recombinant proteins and to avoid the possible loss of biologic activity by the purification process. We evaluated the transcriptional signaling and antiviral activity of IFN-kappa in parallel with IFN-alpha2b with mammalian expression vectors to express each protein transiently. Both IFN-kappa and IFN-alpha2b exhibited comparable transcriptional and antiviral activities. However, in contrast to IFN-alpha2b transcriptional signaling and antiviral activity, IFN-kappa activity was not detectable in conditioned cell culture medium. Subsequent experiments revealed there was a direct relationship between IFN-kappa-expressing cells and antiviral activity. These results were confirmed in immunocytochemical studies. Furthermore, IFN-kappa exhibited cell-associated antiviral activity against a hepatitis C virus (HCV) replicon cell line. This novel IFN signaling strategy may represent an important distinct and divergent mechanism for limiting viral infections.

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“…Murine C57BL/6 B16F0 aggressive melanoma cells were grown in DMEM supplemented with 10% FCS. Monoclonal murine C57BL/6 bone-marrow-derived MSCs were obtained as previously described [ 8 , 10 ], and were grown in DMEM supplemented with 10% fetal bovine serum and 10 ng/ml human basic fibroblast growth factor, obtained from Peprotech (Rocky Hill, NJ, USA). FCS was obtained from Gemini BioProducts (Sacramento, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Our laboratory demonstrated that injection of B16 cells that ectopically express Mu-IFNαA fail to grow to become palpable tumors [ 9 ]. The same is true of B16 cells ectopically expressing Mu-IFNγ and Mu-IFNλ2 [ 10 , 11 ]; notably, these three interferons bind to distinct receptors, act under distinct situations, and exhibit distinct physiological functions. Additionally, the effects of interferon on tumor growth suppression are not restricted to the tumor cells themselves.…”

Section: Introductionmentioning

confidence: 99%

Efficient co-expression of bicistronic proteins in mesenchymal stem cells by development and optimization of a multifunctional plasmid

Krause¹,

Izotova²,

Ren³

et al. 2011

Stem Cell Res Ther

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IntroductionLocal synthesis of interferon within B16 tumors mediates anti-tumor effects. Based on reports that stem cells are recruited to tumors, and because systemic administration of interferon causes dose-limiting undesirable side effects, we wanted to improve the anti-tumor effects of interferon while simultaneously minimizing its systemic side effects by employing mesenchymal stem cells (MSCs) as tumor-localized ectopic producers of interferon. Many vectors exist to fulfill this purpose, but their transfection efficiency and resulting expression levels vary considerably.MethodsTo follow both the recruitment to tumors and the synthesis of interferon by MSCs, we designed a bicistronic vector system that permits fluorescent visualization of vector-transfected and interferon-producing MSCs. We used Mu-IFNαA cDNA as the first cistron and the cherry fluorescent protein cDNA as the second cistron, whose translation requires the internal ribosome entry sequence (IRES) from the encephalomyocarditis virus 5' untranslated region. Observing inconsistent expression of these cistrons in various vectors and cell lines, especially compared with a control plasmid pmaxGFP, we optimized the expression of this bicistronic message by mutating pcDNA3 to facilitate exchange of the promoter and polyadenylation segments controlling both the gene of interest and the eukaryotic antibiotic resistance gene as well as the eukaryotic antibiotic resistance gene itself, and effectively compare the effects of these exchanges, creating plasmid pc3.5.ResultsMurine MSCs stably and ectopically expressing Mu-IFNαA inhibited the establishment of tumors in homogeneic C57/BL6 mice. Mu-IFNαA expressed from the bicistronic message is fully biologically active, but is expressed at only two-thirds of the level observed from a monocistronic message. Cap-dependent translation is threefold more efficient than IRES-driven translation in 293T, B16, and MSC cell lines. Both efficient expression and good transfection efficiency require strong expression of the gene of interest and a chimeric intron. High doses of Mu-IFNαA within tumors inhibited tumor establishment but may not inhibit tumor growth.ConclusionsOur modified vector and its derived plasmids will find use in stem cell therapeutics, gene expression, mRNA regulation, and transcription regulation. Local release of Mu-IFNαA within tumors may differently affect tumor establishment and tumor growth.

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Ifn-Gamma and B7 as Costimulators of Antitumor Immune-Responses

Cited by 4 publications

References 0 publications

Activation of liver X receptor inhibits the development of pulmonary carcinomas induced by 3-methylcholanthrene and butylated hydroxytoluene in BALB/c mice

Activation of liver X receptor inhibits the development of pulmonary carcinomas induced by 3-methylcholanthrene and butylated hydroxytoluene in BALB/c mice

Antiviral Activity of Transiently Expressed IFN-κ Is Cell-Associated

Efficient co-expression of bicistronic proteins in mesenchymal stem cells by development and optimization of a multifunctional plasmid

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