J Chen1, H Niu, W He, D Ba. 1. Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, People's Republic of China.
Abstract
BACKGROUND: The objective of this study was to investigate the antitumor activity of selectively expanded gammadelta T cells in tumor-infiltrating lymphocytes (gammadeltaTILs) or tumor ascites lymphocytes (gammadeltaTALs) from patients with colorectal and ovarian epithelial carcinoma (OEC) in vitro and in vivo. METHODS: gammadeltaTILs/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 gammadeltaTILs 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-alpha and INF-gamma, could promote the cytotoxicities of gammadeltaTILs to tumor cells, whereas IL-10, GM-CSF and TFG-beta had no effect on such killing activities. Rested gammadeltaTILs 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 gammadeltaTILs. Either alphabetaTILs or gammadeltaTILs from patients with OEC displayed cytotoxicities to allogeneic or autologous OEC cell lines at a similar strength in vitro. Transferring gammadeltaTILs 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 alphabetaTILs 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 gammadeltaTIL-treated mice. Similarly, adoptive gammadeltaTALs from the ascites of patients with OEC transferred into nude mice displayed a stronger antitumor response to OEC SKOV3 cells than alphabetaTALs in vivo. Tumor volumes in gammadeltaTAL-treated mice were smaller than in alphabetaTAL-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 gammadeltaTAL-treated nude mice. CONCLUSION: Taken together, our results suggest that gammadeltaT cells could be a new candidate for adoptive immunotherapy in the future treatment of patients with cancer. Copyright 2001 S. Karger AG, Basel.
BACKGROUND: The objective of this study was to investigate the antitumor activity of selectively expanded gammadelta T cells in tumor-infiltrating lymphocytes (gammadeltaTILs) or tumor ascites lymphocytes (gammadeltaTALs) from patients with colorectal and ovarian epithelial carcinoma (OEC) in vitro and in vivo. METHODS: gammadeltaTILs/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 gammadeltaTILs from colorectal tumors demonstrated marked cytotoxicities to allogeneic humancolon adenocarcinoma HR8348 and lymphoma Daudi cells, as well as xenogeneic murinethymoma EL-4 cell lines. Cytokines, including IL-2, IL-4, IL-12, IL-15, TNF-alpha and INF-gamma, could promote the cytotoxicities of gammadeltaTILs to tumor cells, whereas IL-10, GM-CSF and TFG-beta had no effect on such killing activities. Rested gammadeltaTILs 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 gammadeltaTILs. Either alphabetaTILs or gammadeltaTILs from patients with OEC displayed cytotoxicities to allogeneic or autologous OEC cell lines at a similar strength in vitro. Transferring gammadeltaTILs 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 alphabetaTILs 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 gammadeltaTIL-treated mice. Similarly, adoptive gammadeltaTALs from the ascites of patients with OEC transferred into nude mice displayed a stronger antitumor response to OEC SKOV3 cells than alphabetaTALs in vivo. Tumor volumes in gammadeltaTAL-treated mice were smaller than in alphabetaTAL-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 gammadeltaTAL-treated nude mice. CONCLUSION: Taken together, our results suggest that gammadeltaT cells could be a new candidate for adoptive immunotherapy in the future treatment of patients with cancer. Copyright 2001 S. Karger AG, Basel.
Authors: Jörg C Hoffmann; Nina N Pawlowski; Katja Grollich; Christoph Loddenkemper; Martin Zeitz; Anja A Kühl Journal: Int J Colorectal Dis Date: 2008-07-23 Impact factor: 2.571
Authors: Nicholas A Zumwalde; Akshat Sharma; Xuequn Xu; Shidong Ma; Christine L Schneider; James C Romero-Masters; Amy W Hudson; Annette Gendron-Fitzpatrick; Shannon C Kenney; Jenny E Gumperz Journal: JCI Insight Date: 2017-07-06