Effector cells derived from naive T cells used in tumor immunotherapy of mice bearing B16 melanoma

作者：Ming Wen, Weili Xu, Lili Ren, Fei Gao, Naipeng Cui, Junye Wen, Xin-Jiang Li, Lin Lin, Zhenfeng Ma, Baoping Chen, Jianhui Cai · 发表于：Chinese Medical Journal · 年份：2014 · DOI：10.3760/cma.j.issn.0366-6999.20123364 · 被引用次数：1 · 研究领域：CAR-T cell therapy research、Immunotherapy and Immune Responses、Immune Cell Function and Interaction

BACKGROUND: Adoptive cell transfer (ACT) immunotherapy has been used clinically for years to treat malignancies. Improving the killing efficiency of effector cells, such as tumor-specific cytotoxic T lymphocytes (CTLs), is an important component for enhancing the clinical response of cancer immunotherapy. Hence, we explored a novel method for preparing cancer-specific CTLs using naive T lymphocytes. METHODS: C57BL/6 mice bearing B16 melanoma tumors were pretreated with cyclophosphamide (CTX) by peritoneal injection. The immunosuppressive influence of CTX on tumor regression and the tumor microenvironment was assessed. Naive T cells and T cell pools were isolated via negative selection using immunomagnetic beads. The proliferative potential and cytokine production of different T cell subpopulations were evaluated in vitro. Tumor-specific CTLs derived from naive T cells (naive CD4+ T cells: naive CD8+ T cells = 2:1) and pooled T cells were generated in vitro, respectively. B16 melanoma-bearing C57BL/6 mice were pretreated with CTX, followed by ACT immunotherapy using dendritic cell-induced CTLs. The homing abilities of the effector cells and interleukin-2 (IL-2), interferon-γ, granzyme B, and perforin mRNA levels in tumor tissues were evaluated, and the change in tumor volume was measured. RESULTS: Mice receiving CTX peritoneal pretreatment injections did not display tumor regression compared with control mice. However, a significant downregulation of splenic Tregs and tumor gr...