English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Blocking an adhesion molecule on the surface of T cells may enhance antitumor activity. Sticking it to T cells Because of its immunosuppressive effects and abundance in tumor microenvironments, the cytokine transforming growth factor–β (TGF-β) inhibits the antitumor activities of T cells. Targeting TGF-β systemically would interfere with other functions of TGF-β; thus, therapies that block the effects of TGF-β specifically on T cells are needed. Newman et al. found that T cells without the adhesion molecule PECAM-1 were less sensitive to the TGF-β–mediated inhibition of their function than were PECAM-1–positive cells. In a tumor model, PECAM-1–deficient mice exhibited reduced tumor size compared to wild-type mice. Thus, targeting PECAM-1 may specifically enhance the antitumor activity of T cells. Transforming growth factor–β (TGF-β) is an immunosuppressive cytokine that inhibits the proinflammatory functions of T cells, and it is a major factor in abrogating T cell activity against tumors. Canonical TGF-β signaling results in the activation of Smad proteins, which are transcription factors that regulate target gene expression. We found that the cell surface molecule platelet endothelial cell adhesion molecule-1 (PECAM-1) facilitated noncanonical (Smad-independent) TGF-β signaling in T cells. Subcutaneously injected tumor cells that are dependent on TGF-β–mediated suppression of immunity for growth grew more slowly in PECAM-1−/− mice than in their wild-type counterparts. T cells isolated from PECAM-1−/− mice demonstrated relative insensitivity to the TGF-β–dependent inhibition of interferon-γ (IFN-γ) production, granzyme B synthesis, and cellular proliferation. Similarly, human T cells lacking PECAM-1 demonstrated decreased sensitivity to TGF-β in a manner that was partially restored by reexpression of PECAM-1. Co-incubation of T cells with TGF-β and a T cell–activating antibody resulted in PECAM-1 phosphorylation on an immunoreceptor tyrosine–based inhibitory motif (ITIM) and the recruitment of the inhibitory Src homology 2 (SH2) domain–containing tyrosine phosphatase-2 (SHP-2). Such conditions also induced the colocalization of PECAM-1 with the TGF-β receptor complex as identified by coimmunoprecipitation, confocal microscopy, and proximity ligation assays. These studies indicate a role for PECAM-1 in enhancing the inhibitory functions of TGF-β in T cells and suggest that therapeutic targeting of the PECAM-1–TGF-β inhibitory axis represents a means to overcome TGF-β–dependent immunosuppression within the tumor microenvironment.

The adhesion molecule PECAM-1 enhances the TGF-β–mediated inhibition of T cell function