Antitumor effects of human antithymocyte globulin on peripheral T cell lymphoma via complement-dependent and -independent cytotoxicity in xenograft mouse models.

Peripheral T cell lymphomas (PTCL) is a group of non-Hodgkin lymphomas characterized by substantial molecular heterogeneity, rapid progression, poor therapeutic response, and unfavorable outcomes. In recent clinical studies, antithymocyte globulin (ATG)-based allogeneic hematopoietic stem cell transplantation (allo-HSCT) has markedly improved the prognosis and survival of patients with PTCL. This study aimed to explore whether ATG has toxic effects on PTCL cells and evaluate whether ATG combined with chemotherapy has a synergistic antitumor effect. Our research revealed that ATG significantly inhibited PTCL cell growth by suppressing cell proliferation and colony formation. Moreover, ATG treatment decreased cell invasion; however, it had no effect on cell cycle arrest in PTCL cells. ATG-induced PTCL cell apoptosis, which was partially reversed by pan-caspase inhibitor and caspase 8 inhibitor. Additionally, ATG was able to induce complement-dependent cytotoxicity in PTCL cells. Of note, the combination of ATG and doxorubicin exhibited an enhanced antitumor effect against PTCL in xenograft mouse models in vivo. The addition of ATG into the chemotherapy regimen may be a beneficial way for treating PTCL.