Taken together, these data suggest that the discordant regulation of interferon and IL-4 pathway genes by EBV that occurs early following infection of B cells has relevance to the development or maintenance of an EBV-associated malignancy.
Experimental models of vaccination with tumor cells engineered to produce interleukin-4 (IL-4) have shown that the local release of this cytokine is associated with the development of antitumor immunity that may induce regression of established cancer.
It has previously been shown that murine sarcoma cells express high-affinity IL-4 receptors (IL-4R) which are internalized after binding to the ligand (Puri et al., Cancer Res 1991; 51:3011-7).
In combined analyses using data from previous studies, we found that the risk of gastric non-cardia cancer development was significantly associated with IL-4-168 C allele (OR: 0.81, 95% CI: 0.69-1.00) and IL-4-590 T allele carrier status (0.61, 0.53-0.73), and IL-6-174 G/G genotype (2.02, 1.31-3.10).
By integrating the overrepresented pathways such as pathways in cancer, epithelial growth factor receptor, c-Met, interleukin-4 (IL-4) and IL-6 signaling pathways, along with a set of proteins (e.g. phospholipase D (PLD), IL-4 receptor, IL-17 receptor, laminins, collagens, and mucins) into the PLD pathway and inflammatory cytokines network as the most critical events in both groups, two super networks were made to elucidate new aspects of NSCLC pathogenesis and to determine the influence of cigarette smoking on tumour formation.
AP-2alpha, interleukin-4 (IL-4), E-cadherin, fibulin 1D, p16(INK4alpha), PTEN, RKIP, and S100A4 are determinants (suppressors, except for S100A4) of cancer cell invasiveness and other traits of cancer progression, which are located upstream of matrix metalloproteinases (MMPs) in cell signaling pathways.
These findings suggest that IL4 from Tfh cells affects antitumor immunity and constitutes an attractive therapeutic target to reduce immunosuppression in the tumor microenvironment, and thus enhance the efficacy of cancer immunotherapy.Cancer .
In vivo transfection and/or cross-priming of dendritic cells following DNA and adenoviral immunizations for immunotherapy of cancer--changes in peripheral mononuclear subsets and intracellular IL-4 and IFN-gamma lymphokine profile.
The binding of [AP1-V12]6 to cancer cells was remarkably reduced when IL-4 receptors were blocked by antibody against IL-4 receptor further confirmed its binding.
The degree of fibrocyte expansion observed in individual subjects directly correlated with the frequency of circulating GATA3⁺CD4⁺ cells (R = 0.80) and monocytes from healthy donors cultured with IL-4 differentiated into fibrocytes with the same phenotypic profile and immunosuppressive properties as those observed in patients with cancer.
Interleukin-4 plays a critical role in the regulation of immune responses and has been detected at high levels in the tumour microenvironment of cancer patients, where concentrations correlate with the grade of malignancy.
The results suggested that there was no significant association between IL-4-590C/T polymorphism and cancer risks (TT + TC vs. CC: OR = 0.97, 95 % CI = 0.90-1.04, P = 0.36).
To assess the relationship between IL-4 polymorphisms and cancer risks, we performed a meta-analysis which includes 14 studies involving 3,562 cancer cases for IL-4 rs2243250 polymorphism, 6 studies involving 2,052 subjects for IL-4 rs2070874 polymorphism, and 5 studies involving 791 subjects for IL-4 intron-3 polymorphism.
Loss of tumorigenicity of human pancreatic carcinoma cells engineered to produce interleukin-2 or interleukin-4 in nude mice: a potentiality for cancer gene therapy.
Since then, new roles for IL-4 and IL-13 and their receptors in normal gestation, fetal development and neurological function and in the pathogenesis of cancer and fibrosis have been appreciated.
Among different subtypes of GC, a higher risk of developing diffuse type (OR 1.64, 95% CI 1.01-2.67) or cardia cancer (OR 2.44, 95% CI 1.13-2.67) was observed for the CT/CC genotype of IL-4 at the position -590, whereas the high IL-10 producer genotype was significantly linked with the risk of cardia cancer (OR 3.21, 95% CI 1.06-9.73) or advanced stage (OR 2.29, 95% CI 1.12-4.64).
Human autologous dermal fibroblasts have been cultured, transduced with the interleukin-4 (IL-4) gene and used as a vaccine together with irradiated autologous tumor cells in patients with cancer participating in a phase I/II clinical trial at the University of Pittsburgh Cancer Institute.
The concentrations of IL13, IL10 and IL4 were significantly lower in group with positive history of cancer compared to group with negative history of cancer.