Anti-tumor effects of human peripheral gamma delta T cells in a mouse tumor model

Peripheral gamma delta T cells derived from healthy donors were found to ex hibit cytotoxicity against a variety of tumor cell lines in vitro, includin g CNE2, which was established from nasopharyngeal carcinoma (NPC), The anti -tumor effects were further studied in a mouse model. Control nude mice ino culated s.c. with 5 x 10(6) CNE2 cells regularly developed hypodermal tumor s, which progressively increased in size, and animals had a mean survival o f 35 +/- 3.4 days. Tumor growth was arrested and tumor size was reduced aft er animals were infused with 5 x 10(7) gamma delta T cells derived from a h ealthy donor. The anti-tumor effects were temporary. however, and tumor gro wth was resumed after about I week in a group of the animals that had been given a single dose of gamma delta T cells. In another group of animals giv en 2 doses of gamma delta cells I week apart, resumption of tumor growth wa s delayed for a further week. Mean survival of the 2 groups was increased t o 61 +/- 15.7 and 74 +/- 12.9 days, respectively, Immunohistology revealed an accumulation of infused cells in tumors attended by focal tumor necrosis in specimens taken 2 days after infusion, Infiltrative cells virtually dis appeared from tumor tissues 6 days after infusion, accompanied by increased mitotic indices of tumor cells. These temporal relationships suggested tha t the accumulation of infused gamma delta T cells in hypodermal tumors was responsible for the observed antitumor effects. (C) 2001 Wiley-Liss, Inc.