Antitumour activity of expanded human tumor-infiltrating gamma delta T lymphocytes

Background: The objective of this study was to investigate the antitumor ac tivity of selectively expanded gamma delta T cells in tumor-infiltrating ly mphocytes (gamma delta TILs) or tumor ascites lymphocytes (gamma delta TALs ) from patients with colorectal and ovarian epithelia[ carcinoma (OEC) in v itro and in vivo. Methods: gamma delta TILs/TALs were expanded by the solid -phase antibody method; their cytolytic and proliferative activities in vit ro were detected by the MTT method and H-3-TdR incorporation and their effe ct in vivo was evaluated by the nude mice model. Results: Expanded gamma de lta TILs from colorectal tumors demonstrated marked cytotoxicities to allog eneic human colon adenocarcinoma HR8348 and lymphoma Daudi cells, as well a s xenogeneic murine thymoma EL-4 cell lines. Cytokines, including IL-2, IL- 4, IL-12, IL-15, TNF-alpha and INF-gamma, could promote the cytotoxicities of gamma delta TILs to tumor cells, whereas IL-10, GM-CSF and TFG-beta had no effect on such killing activities. Rested gamma delta TILs could prolife rate 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 o nly cytotoxicity-related antigen recognized by gamma delta TILs. Either alp ha beta TILs or gamma delta TILs from patients with OEC displayed cytotoxic ities to allogeneic or autologous OEC cell lines at a similar strength in v itro. Transferring gamma delta TILs into Daudi cell-bearing BALB/c nude mic e with an injection of IL-2 was able to maintain a high survival rate of th e mice for 30 days, when compared with mice treated with alpha beta TILs or without any treatment (p < 0.05). Without coinjection of IL-2, after 3 mon ths of Daudi tumor inoculation, a high survival rate was observed in,gamma delta TIL-treated mice. Similarly, adoptive gamma delta TALs from the ascit es of patients with OEC transferred into nude mice displayed a stronger ant itumor response to OEC SKOV3 cells than alpha beta TALs in vivo. Tumor volu mes in gamma delta TAL-treated mice were smaller than in alpha beta TAL-tre ated 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 d ecreasing trend of carcinogenic rate was observed in <gamma>delta TAL-treat ed nude mice. Conclusion: Taken together, our results suggest that gamma de ltaT cells could be a new candidate for adoptive immunotherapy in the futur e treatment of patients with cancer. Copyright (C) 2001 S. Karger AG, Basel .