A Synthetic CD8α:MyD88 Coreceptor Enhances CD8⁺ T-cell Responses to Weakly Immunogenic and Lowly Expressed Tumor Antigens.

ABSTRACT: T cell-based immunotherapies are a promising approach for patients with advanced cancers. However, various obstacles limit T-cell efficacy, including suboptimal T-cell receptor (TCR) activation and an immunosuppressive tumor environment. Here, we developed a fusion protein by linking CD8α and MyD88 (CD8α:MyD88) to enhance CD8⁺ T-cell responses to weakly immunogenic and poorly expressed tumor antigens. CD8α:MyD88-engineered T cells exhibited increased proliferation and expression of effector and costimulatory molecules in a tumor antigen-dependent manner. These effects were accompanied by elevated activation of TCR and Toll-like receptor signaling-related proteins. CD8α:MyD88-expressing T cells improved antitumor responses in mice. Enhanced antitumor activity was associated with

SUBMITTER: Kaczanowska S 

PROVIDER: S-EPMC5732881 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature