β-catenin-overexpressed melanoma inhibited IFN-γ production by melanoma-specific CTLs in an IL-10-independent manner and is more resistant to CTL lysis in vitro and in vivo.
We tested IFN-gamma, TNF-alpha and interleukin-2 (IL-2), which are presumably released by infiltrating leukocytes in the melanoma lesional environment, on three melanoma cell lines.
We studied melanoma cell responses to transient exposure to the cytokine interferon γ (IFNγ) by combining a systems-scale analysis of gene expression dynamics with computational modeling and experiments.
We show that interferon-gamma-induced growth inhibition could be abrogated by overexpression of dominant negative STAT1 (signal transducer and activator of transcription 1) in the melanoma cell line A375, suggesting that STAT1 plays a crucial part for the anti-proliferative effect.
We previously reported that interleukin 4 (IL-4) and either tumor necrosis factor alpha (TNF) or interferon gamma (IFN) synergistically inhibit melanoma cell growth and induce cell differentiation.
To determine whether MnSOD plays a role in the antiviral action of IFN-gamma, we employed an antisense strategy to inhibit the expression of MnSOD in the human melanoma cell line, A375.
To assess whether RAS oncogenes may affect the expression of cytokines in tumor cells, the presence of interleukins (IL) 1 alpha, 1 beta, 4, 6, 7, and 8, tumor necrosis factor (TNF) alpha and interferon gamma mRNA has been analyzed by reverse transcriptase-polymerase chain reaction in 19 melanoma clones derived from the metastatic cell line 665/2 and previously characterized for RAS mutation and expression.
This study yielded a panel of melanoma cell lines with different patterns of constitutive and IFN-gamma-induced expression of HLA class II that can be used in future studies of the mechanisms of regulation of HLA class II expression.
These protective effects were long-lasting in Panc02-induced tumor development, but not in melanoma. iDC-vaccination impacted the immune status of the hosts by greatly increasing the percentage of CD8<sup>+</sup> T-cells, and natural killer (NK)1.1<sup>+</sup> cells, that express granzyme B associated with Lamp-1 and IFN-γ.
These observations, together with data obtained comparing the effect of 5-AZA-CdR with that of interferon-gamma, strongly suggest that 5-AZA-CdR may have prospective therapeutic implications in active and/or passive specific immunotherapy for human melanoma.
Therefore, a phase I clinical trial was performed of autologous <i>in vitro</i> expanded iNKT cells in stage IIIB-IV melanoma.<b>Experimental Design:</b> Residual iNKT cells [<0.05% of patient peripheral blood mononuclear cell (PBMC)] were purified from autologous leukapheresis product using an antibody against the iNKT cell receptor linked to magnetic microbeads. iNKT cells were then expanded with CD3 mAb and IL2 <i>in vitro</i> to obtain up to approximately 10<sup>9</sup> cells.<b>Results:</b> Expanded iNKT cells produced IFNγ, but limited or undetectable IL4 or IL10.
The siPD-L1/pd suppressed the expression of PD-L1 in the interferon-γ (IFN-γ)-challenged B16F10 melanoma cells in a cell-type dependent manner and attenuated the expression of tumor-specific genes in B16F10 cells. siPD-L1/pd suppressed the B16F10 melanoma growth in C57BL/6 immune-competent mice with increased tumor-specific immunity. siPD-L1/pd also suppressed melanoma growth in immune-compromised nude mice.
The insertion of the IFN gamma gene into melanoma cells may be useful either for active immunization against melanoma or for the generation of TIL to be used in adoptive immunotherapy.
The aim of the current study was to observe the effects of suppressor of cytokine signaling 1 (SOCS1) silencing in human melanoma cells on cell biological behavior and interferon-γ (IFN-γ) sensitivity, and to investigate the use of SOCS1 as a therapeutic target in the treatment of melanoma.
Suppressor-of-cytokine-2 (SOCS2) protein, a conserved program transcript, is expressed by mononuclear phagocytes infiltrating primary melanoma and is induced by IFNγ.
Over-expression of SOCS proteins in melanoma cell lines led to significant inhibition of Tyr701-phosphorylated STAT1 (P-STAT1) and gene expression following stimulation with IFN-alpha (IFIT2, OAS-1, ISG-15) or IFN-gamma (IRF1).
Our results demonstrate that melanoma responses to IFNγ are heterogeneous, frequently downregulated in immune checkpoint inhibitor-naïve melanoma and potentially predictive of response to immunotherapy.
Our previous works have shown that IL-10 and IFNγ co-regulate indoleamine-2,3-dioxygenase (IDO)-expressing immunosuppressive dendritic cells (DCs) in melanoma SLNs.
Our objective in this study was to investigate whether polymorphisms in the regulatory regions of IL10, IL6 and IFNgamma genes are associated with the development of primary cutaneous melanoma and/or the prognosis of this tumour.