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

Abstract

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 growth factor-β1 (TGF-β1) and interleukin-10 (IL-10) serum levels was observed (P < 0.05). Naive T cells showed a stronger proliferative capacity and elevated cytokine production than did pooled T cells (P < 0.05). In addition, effector cells generated from naive T cells displayed more potent antitumor activity in vivo than those derived from pooled T cells (P < 0.05).

CONCLUSION:

Effector cells derived from the naive T cells possess a stronger proliferative potential, homing capacity, and enhanced cytokine production, which leads to a superior antitumor response.

• Authors: Ming Wen, Weili Xu, Lili Ren, Fei Gao, Naipeng Cui, Junye Wen, Xinjiang Li, Lin Lin, Zhenfeng Ma, Baoping Chen, Jianhui Cai
• Journal: Chinese medical journal (Chin Med J (Engl)) Vol. 127 Issue 7 Pg. 1328-33 ( 2014) ISSN: 2542-5641 [Electronic] China
• PMID: 24709189 (Publication Type: Journal Article)

Topics

• Animals
• Cell Line, Tumor
• Cells, Cultured
• Female
• Flow Cytometry
• Immunotherapy, Adoptive (methods)
• Melanoma, Experimental (therapy)
• Mice, Inbred C57BL