Embryonic Fibroblasts Promote Antitumor Cytotoxic Effects of CD8(+) T Cells

Abstract

Adoptive CD8(+) T cell therapy has emerged as an important modality for the treatment of cancers. However, the significant drawback of transfused T cells is their poor survival and functionality in response to tumors. To overcome this limitation, an important consideration is exploring a culture condition to generate superior antitumor cytotoxic T lymphocytes (CTLs) for adoptive therapy. Here, we provide a novel approach to generate potent CTL clones in mouse embryonic fibroblast-conditioned medium (MEF-CM). We found CTLs derived with MEF-CM have higher potential in long-term persistence in tumor bearing and non-tumor-bearing mice. Importantly, adoptive transfer of MEF-CM-cultured CTLs dramatically regressed tumor growth and prolonged mice survival. Characterization of MEF-CM-cultured CTLs (effector molecules, phenotypes, and transcription factors) suggests that MEF-CM enhances the effector functions of CD8(+) T cells in part by the upregulation of the T-box transcription factor eomesodermin. Consequently, MEF-CM enhances the intrinsic qualities of effector CD8(+) T cells to augment antitumor immunity.