The Antitumor Effects of Vaccine-Activated CD8⁺ T Cells Associate with Weak TCR Signaling and Induction of Stem-Like Memory T Cells.

ABSTRACT: To understand why vaccine-activated tumor-specific T cells often fail to generate antitumor effects, we studied two α-fetoprotein-specific CD8⁺ T cells (Tet₄₉₉ and Tet₂₁₂) that had different antitumor effects. We found that Tet₄₉₉ required high antigen doses for reactivation, but could survive persistent antigen stimulation and maintain their effector functions. In contrast, Tet₂₁₂ had a low threshold of reactivation, but underwent exhaustion and apoptosis in the presence of persistent antigen. In vivo, Tet₄₉₉ cells expanded more than Tet₂₁₂ upon reencountering antigen and generated stronger antitumor effects. The different antigen responsiveness and antitumor effects of Tet₂₁₂ and Tet₄₉₉

SUBMITTER: Wu S 

PROVIDER: S-EPMC5626646 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature