Transfection of the genes for interleukin‐12 into the K1735 melanoma and the EMT6 mammary sarcoma murine cell lines reveals distinct mechanisms of antitumor activity

Moran, James P.; Gerber, Scott A.; Martin, Celeste A.; Frelinger, John G.; Lord, Edith M.

doi:10.1002/ijc.11284

Cited by 7 publications

(4 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The tumor cells themselves appear to contribute to the expression of both MIG and IP-10, as evidenced by the decrease in both chemokine levels in tumors that were incapable of responding to IFN-␥. Production of MIG and IP-10 appears to be a common feature in many tumor cells, as we and others have reported this trait in other tumor lines in vitro (14,24). In addition to recruiting IFN-␥-producing T cells, MIG and IP-10 also have antiangiogenic properties (40).…”

Section: Discussionsupporting

confidence: 52%

Radiation-Induced IFN-γ Production within the Tumor Microenvironment Influences Antitumor Immunity

Lugade

Sorensen

Gerber

et al. 2008

The Journal of Immunology

Self Cite

423

321

View full text Add to dashboard Cite

Alterations to the tumor microenvironment following localized irradiation may influence the effectiveness of subsequent immunotherapy. The objective of this study was to determine how IFN-γ influences the inflammatory response within this dynamic environment following radiotherapy. B16/OVA melanoma cells were implanted into C57BL/6 (wild-type (WT)) and IFN-γ-deficient (IFN-γ−/−) mice. Seven days after implantation, mice received 15 Gy of localized tumor irradiation and were assessed 7 days later. Irradiation up-regulated the expression of VCAM-1 on the vasculature of tumors grown in WT but not in IFN-γ−/− mice. Levels of the IFN-γ-inducible chemokines MIG and IFN-γ-inducible protein 10 were decreased in irradiated tumors from IFN-γ−/− mice compared with WT. In addition to inducing molecular cues necessary for T cell infiltration, surface MHC class I expression is also up-regulated in response to IFN-γ produced after irradiation. The role of IFN-γ signaling in tumor cells on class I expression was tested using B16/OVA cells engineered to overexpress a dominant negative mutant IFN-γ receptor (B16/OVA/DNM). Following implantation and treatment, expression of surface class I on tumor cells in vivo was increased in B16/OVA, but not in B16/OVA/DNM tumors, suggesting IFN-γ acts directly on tumor cells to induce class I up-regulation. These increases in MHC class I expression correlated with greater levels of activated STAT1. Thus, IFN-γ is instrumental in creating a tumor microenvironment conducive for T cell infiltration and tumor cell target recognition.

show abstract

Section: Discussionsupporting

confidence: 52%

Radiation-Induced IFN-γ Production within the Tumor Microenvironment Influences Antitumor Immunity

Lugade

Sorensen

Gerber

et al. 2008

The Journal of Immunology

Self Cite

423

321

View full text Add to dashboard Cite

show abstract

“…2A, second rung ). Such phenomenon of delayed regression following maximum growth has never been observed in IL-12-transfected melanoma cells by us (25) and other investigators (26,27). Thus, IL-23-mediated tumor regression seems to be quite unique.…”

Section: Discussionmentioning

confidence: 63%

Interleukin-23 and Interleukin-27 Exert Quite Different Antitumor and Vaccine Effects on Poorly Immunogenic Melanoma

Oniki¹,

Nagai²,

Horikawa³

et al. 2006

Cancer Research

126

114

View full text Add to dashboard Cite

Recent studies revealed that two novel interleukin (IL)-12-related cytokines, IL-23 and IL-27, have potent antitumor activities. However, the antitumor effects were mainly evaluated in relatively highly immunogenic tumors and have not been fully evaluated against nonimmunogenic or poorly immunogenic tumors. In this study, we investigated the antitumor efficacies of IL-23 and IL-27 on poorly immunogenic B16F10 melanoma and found that the antitumor responses mediated by IL-23 and IL-27 were clearly different. In syngeneic mice, mouse single-chain (sc) IL-23-transfected B16F10 (B16/IL-23) tumors exhibited almost the same growth curve as B16F10 parental tumor about until day 20 after tumor injection and then showed growth inhibition or even regression. In contrast, scIL-27-transfected B16F10 (B16/ IL-27) tumors exhibited significant retardation of tumor growth from the early stage. In vivo depletion assay revealed that the antitumor effect of B16/IL-23 was mainly mediated by CD8 + T cells and IFN-; whereas that of B16/IL-27 mainly involved natural killer cells and was independent of IFN-;. We also found that antitumor effects of B16/IL-23 and B16/IL-27 were synergistically enhanced by treatment with IL-18 and IL-12, respectively. Furthermore, B16/IL-23-vaccinated mice developed protective immunity against parental B16F10 tumors but B16/IL-27-vaccinated mice did not. When combined with prior in vivo depletion of CD25 + T cells, 80% of B16/ IL-23-vaccinated mice completely rejected subsequent tumor challenge. Finally, we showed that the systemic administration of neither IL-23 nor IL-27 induced such intense toxicity as IL-12. Our data support that IL-23 and IL-27 might play a role in future cytokine-based immunotherapy against poorly immunogenic tumors. (Cancer Res 2006; 66(12): 6395-404)

show abstract

“…Whole-mount histology previously described for mice (17,24,25) was adapted for use in Xenopus. Briefly, skin transplants with a bit of surrounding host skin were harvested from anesthetized animals, washed gently in ice-cold amphibian phosphate-buffered saline (APBS), and transferred to 5 mL polystyrene round-bottom tubes (Falcon, BD).…”

Section: Whole-mount Immunohistochemistrymentioning

confidence: 99%

In Vivo Study of T-Cell Responses to Skin Alloantigens in Xenopus Using a Novel Whole-Mount Immunohistology Method

et al. 2007

Self Cite

View full text Add to dashboard Cite

show abstract

Transfection of the genes for interleukin‐12 into the K1735 melanoma and the EMT6 mammary sarcoma murine cell lines reveals distinct mechanisms of antitumor activity

Cited by 7 publications

References 50 publications

Radiation-Induced IFN-γ Production within the Tumor Microenvironment Influences Antitumor Immunity

Radiation-Induced IFN-γ Production within the Tumor Microenvironment Influences Antitumor Immunity

Interleukin-23 and Interleukin-27 Exert Quite Different Antitumor and Vaccine Effects on Poorly Immunogenic Melanoma

In Vivo Study of T-Cell Responses to Skin Alloantigens in Xenopus Using a Novel Whole-Mount Immunohistology Method

Contact Info

Product

Resources

About