CD137 and CD137L signals are main drivers of type 1, cell-mediated immune responses

Abstract

CD137 is expressed on activated T cells and NK cells, among others, and is a potent co-stimulator of antitumor immune responses. CD137 ligand (CD137L) is expressed by antigen presenting cells (APC), and CD137L reverse signaling into APC enhances their activity. CD137-CD137L interactions as main driver of type 1, cell-mediated immune responses explains the puzzling observation that CD137 agonists which enhance antitumor immune responses also ameliorate autoimmune diseases. Upon co-stimulation by CD137, Th1 CD4 T cells together with Tc1 CD8 T cells and NK cells inhibit other T cell subsets, thereby promoting antitumor responses and mitigating non-type 1 auto-immune diseases.

Effects of equibiaxial mechanical stretch on extracellular matrix‐related gene expression in human calvarial osteoblasts

“…A reduction in the activity of caspase 3 in this study is therefore consistent with the increased expression of DFF45 . Another apoptosis‐related gene that was upregulated in a time‐dependent manner is TNFRSF9 , which stimulates the activity of activated T cells and enhances T‐cell proliferation ; however, in vitro, TNFRSF9 expression on activated endothelial cells can enhance the adhesion of monocytes under defined flow conditions . The TNFRSF9 protein has mainly been reported to mediate immune responses but not act on osteoblasts.…”

The relevance of soluble CD137 in the regulation of immune responses and for immunotherapeutic intervention

“…CD137 activation not only costimulates T cell activity but also polarizes T helper cells toward a Th1 response and strongly activates cytotoxic T cells resulting in a Th1/Tc1 shift . These two effector functions are essential to antitumor immunotherapy and form the basis for the antitumor activities of CD137 agonists.…”

Artificial antigen-presenting cells are superior to dendritic cells at inducing antigen-specific cytotoxic T lymphocytes

“…Signaling through 4-1BB by its natural ligand, 4-1BB-L, or an agonistic antibody, promotes T cell expansion, and sustains their survival and enhances their cytolytic effector functions [24]. CD80/CD28 co-stimulation is critical for efficient Th1 responses.…”