Antitumor Activity of Expanded Human Tumor-Infiltrating γδ T Lymphocytes

Abstract

Background: The objective of this study was to investigate the antitumor activity of selectively expanded γδ T cells in tumor-infiltrating lymphocytes (γδTILs) or tumor ascites lymphocytes (γδTALs) from patients with colorectal and ovarian epithelial carcinoma (OEC) in vitro and in vivo. Methods: γδTILs/TALs were expanded by the solid-phase antibody method; their cytolytic and proliferative activities in vitro were detected by the MTT method and ³H-TdR incorporation and their effect in vivo was evaluated by the nude mice model. Results: Expanded γδTILs from colorectal tumors demonstrated marked cytotoxicities to allogeneic human colon adenocarcinoma HR8348 and lymphoma Daudi cells, as well as xenogeneic murine thymoma EL-4 cell lines. Cytokines, including IL-2, IL-4, IL-12, IL-15, TNF-α and INF-γ, could promote the cytotoxicities of γδTILs to tumor cells, whereas IL-10, GM-CSF and TFG-β had no effect on such killing activities. Rested γδTILs could proliferate strongly in response to mitomycin C-treated Daudi and EL-4 tumor cells, but not to HR8348 tumor cells, suggesting that the latter might possess only cytotoxicity-related antigen recognized by γδTILs. Either αβTILs or γδTILs from patients with OEC displayed cytotoxicities to allogeneic or autologous OEC cell lines at a similar strength in vitro. Transferring γδTILs into Daudi cell-bearing BALB/c nude mice with an injection of IL-2 was able to maintain a high survival rate of the mice for 30 days, when compared with mice treated with αβTILs or without any treatment (p < 0.05). Without coinjection of IL-2, after 3 months of Daudi tumor inoculation, a high survival rate was observed in γδTIL-treated mice. Similarly, adoptive γδTALs from the ascites of patients with OEC transferred into nude mice displayed a stronger antitumor response to OEC SKOV3 cells than αβTALs in vivo. Tumor volumes in γδTAL-treated mice were smaller than in αβTAL-treated or non-TAL-treated mice within the period from day 23 to day 50 after tumor inoculation (p < 0.05). Fifty days after SKOV3 tumor inoculation, a decreasing trend of carcinogenic rate was observed in γδTAL-treated nude mice. Conclusion: Taken together, our results suggest that γδT cells could be a new candidate for adoptive immunotherapy in the future treatment of patients with cancer.