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.
Bibliographical noteFunding Information:
We thank crews of Geyrim Experimental Animal Resource Center for their assistance in animal handling and maintenance. This work was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF-2015R1A2A2A01008124).
© 2018 Qin, Shin, Yoon and Park.
- Adoptive T cell therapy
- CD8 T cells
- Cytotoxic T lymphocytes
- Long-term persistence
- Mouse embryonic fibroblast-conditioned medium
ASJC Scopus subject areas
- Immunology and Allergy