Hua Li1, Yubin Wang, FuXiang Zhou. 1. Department of Medicine Oncology and Radiation Oncology, Zhongnan Hospital, Wuhan University, PR China.
Abstract
OBJECTIVE: To investigate the antitumor activity of ex vivo-expanded γδ-T cells derived from tumor-infiltrating lymphocytes(γδTILs) from cervical cancer patients when combined with galectin-1 antibody and studied both in vitro and in vivo. METHODS: The presence of γδTILs in cervical cancer specimens was detected by immunohistochemistry and γδTILs were expanded using the solid-phase antibody method. The expression of galectin-1 by the human cervical cancer cell line, SiHa, was measured by Western blot and ELISA. In vitro cytotoxic activities of expanded γδTILs, with or without galectin-1 inhibitor, were determined using the LDH-release test. In vivo antitumor activity of γδTILs, combined with galectin-1 antibody, was evaluated using the SCID mouse model. RESULTS: γδTILs existed in the cervical cancer and the percentage of TCRγδ(+) cells in γδTILs after ex vivo expansion was 91.2±1.2% detected by flow cytometry. SiHa cell expressed and secreted galectin-1 as measured by Western blot and ELISA. Expanded γδTILs from human cervical cancer demonstrated marked cytotoxicity to SiHa or Hela cells. In comparison with non-treated group, the cytotoxicity of γδ TILs towards SiHa or Hela cell was significantly increased when effector and target cells were incubated with either lactose or galectin-1 antibody at E/T ratio of 1:1 (p < 0.05). γδTILs, in combination with galectin-1 antibody treatment, significantly suppressed the growth of xenografts in SCID mice, in comparison with all other groups (p < 0.05). γδTILs alone also showed the ability to inhibit tumour growth in vivo, but were more efficient when combined with specific antibody (p < 0.05). CONCLUSION: Taken together, our results suggest that γδ-T cells, combined with galectin-1 antibody treatment, could be a more effective adoptive immunotherapy for patients with cervical cancer than traditional adoptive immunotherapy methods.
OBJECTIVE: To investigate the antitumor activity of ex vivo-expanded γδ-T cells derived from tumor-infiltrating lymphocytes(γδTILs) from cervical cancerpatients when combined with galectin-1 antibody and studied both in vitro and in vivo. METHODS: The presence of γδTILs in cervical cancer specimens was detected by immunohistochemistry and γδTILs were expanded using the solid-phase antibody method. The expression of galectin-1 by the humancervical cancer cell line, SiHa, was measured by Western blot and ELISA. In vitro cytotoxic activities of expanded γδTILs, with or without galectin-1 inhibitor, were determined using the LDH-release test. In vivo antitumor activity of γδTILs, combined with galectin-1 antibody, was evaluated using the SCIDmouse model. RESULTS: γδTILs existed in the cervical cancer and the percentage of TCRγδ(+) cells in γδTILs after ex vivo expansion was 91.2±1.2% detected by flow cytometry. SiHa cell expressed and secreted galectin-1 as measured by Western blot and ELISA. Expanded γδTILs from humancervical cancer demonstrated marked cytotoxicity to SiHa or Hela cells. In comparison with non-treated group, the cytotoxicity of γδ TILs towards SiHa or Hela cell was significantly increased when effector and target cells were incubated with either lactose or galectin-1 antibody at E/T ratio of 1:1 (p < 0.05). γδTILs, in combination with galectin-1 antibody treatment, significantly suppressed the growth of xenografts in SCIDmice, in comparison with all other groups (p < 0.05). γδTILs alone also showed the ability to inhibit tumour growth in vivo, but were more efficient when combined with specific antibody (p < 0.05). CONCLUSION: Taken together, our results suggest that γδ-T cells, combined with galectin-1 antibody treatment, could be a more effective adoptive immunotherapy for patients with cervical cancer than traditional adoptive immunotherapy methods.