Anti-CD3/Anti-CD28 Bead Stimulation Overcomes CD3 Unresponsiveness in Patients With Head and Neck Squamous Cell Carcinoma

Abstract

THE INDUCTION of a T-cell immune response by antigen-presenting cells (APCs) occurs in 3 distinct stages. Initially, a nonspecific adhesion occurs between an APC and a T cell; next, the antigen–major histocompatibility complex of the APC crosslinks with the T-cell receptor (TcR). The final step occurs when a second or costimulatory signal is delivered by the APC to the T cell, enhancing stimulation. At present, the best-characterized second signal occurs when the B7.1 or B7.2 ligand of the APC binds to the CD28 receptor of the T cell, resulting in enhanced cellular activation.1 The immune response initiated may be characterized as a type 1 (TH1) or 2 (TH2) response based on the cytokines secreted from CD4+ T cells. A TH1 response is characterized by the secretion of interleukin (IL)–2, tumor necrosis factor α (TNF-α), and interferon γ (IFN-γ) and represents a delayed hypersensitivity type of response or cytotoxic response against cancer or microbes. A TH2 response is characterized by the secretion of IL-4, IL-5, IL-6, IL-10, and IL-13 and enhances antibody production from B cells as well as an allergic response.2