Immune network theory: a role for parallel distributed processing?

BACKGROUND: Several reports suggest that the dissemination of neoplastic cells and cancer progression are associated with the generation of an immunosuppressive environment. METHODS: In this report, we investigated immunological effects of prostate cancer by comparing metastastic and non-metastatic pelvic lymph nodes (LNs) from 25 patients with carcinomatous involvement of LNs to the non-metastatic LNs from 26 control patients with no metastatic involvement by immunohistochemistry and histological analyses. RESULTS: Our results showed a decreased abundance of CD20+ B lymphocytes (P = 0.031), CD38+ activated lymphocytes (P = 0.038), and CD68+ macrophages (P < 0.001), and less evidence of follicular hyperplasia (P = 0.014), sinus hyperplasia (P < 0.001), and fibrosis (P=0.028) in metastatic LNs comparatively to control LNs. Finally, we observed that metastatic LNs were significantly smaller than control LNs (P = 0.005). CONCLUSIONS: Our results suggest that the development of prostate cancer LN metastasis is accompanied with smaller LN size and decreased LN reactivity suggesting the development of an immununosuppressive microenvironment.

B-Lymphocytes↗

PubMed2006

Global mapping of c-Myc binding sites and target gene networks in human B cells.

The protooncogene MYC encodes the c-Myc transcription factor that regulates cell growth, cell proliferation, cell cycle, and apoptosis. Although deregulation of MYC contributes to tumorigenesis, it is still unclear what direct Myc-induced transcriptomes promote cell transformation. Here we provide a snapshot of genome-wide, unbiased characterization of direct Myc binding targets in a model of human B lymphoid tumor using ChIP coupled with pair-end ditag sequencing analysis (ChIP-PET). Myc potentially occupies > 4,000 genomic loci with the majority near proximal promoter regions associated frequently with CpG islands. Using gene expression profiles with ChIP-PET, we identified 668 direct Myc-regulated gene targets, including 48 transcription factors, indicating that Myc is a central transcriptional hub in growth and proliferation control. This first global genomic view of Myc binding sites yields insights of transcriptional circuitries and cis regulatory modules involving Myc and provides a substantial framework for our understanding of mechanisms of Myc-induced tumorigenesis.

B-Lymphocytes↗

PubMed2006

Modulation of the human cytokine response by interferon lambda-1 (IFN-lambda1/IL-29).

The interferon lambda family (IFN-lambda1/2/3) is a newly described group of cytokines that are related to both the type-1 interferons and IL-10 family members. These novel cytokines are induced during viral infection and, like type-1 interferons, display significant anti-viral activity. In order to understand their function in more depth, we have examined the ability of IFN-lambda1/IL-29 to regulate cytokine production by human immune cells. Whole peripheral blood mononuclear cells (PBMC) exposed to IFN-lambda1 specifically upregulated IL-6, -8 and -10 but there were no visible effects on TNF or IL-1. This response was produced in a dose-dependant fashion and was inhibited by IL-10. Examination of purified cell populations isolated from PBMC demonstrated that monocytes, rather than lymphocytes, were the major IFN-lambda1-responsive cellular subset, producing IL-6, -8 and -10 in response to IFN-lambda1. Monocyte responses induced by low-level LPS stimulation were also synergistically enhanced by the presence of IFN-lambda1. Human macrophages were also shown to react to IFN-lambda1 similarly to monocytes, by producing the cytokines IL-6, -8 and -10. In conclusion, we have shown that IFN-lambda1, a cytokine produced in response to viral infection, activates both monocytes and macrophages producing a restricted panel of cytokines and may therefore be important in activating innate immune responses at the site of viral infection.

B-Lymphocytes↗