PMID: 9531305Apr 8, 1998Paper

Purification of L-selectin(low) cells promotes the generation of highly potent CD4 antitumor effector T lymphocytes

The Journal of Immunology : Official Journal of the American Association of Immunologists
H Kagamu, S Shu

Abstract

Successful adoptive immunotherapy of cancer requires the identification, isolation, and expansion of tumor-specific immune effector cells. A reliable source of tumor-immune lymphocytes is lymph nodes draining a growing tumor. After in vitro stimulation with anti-CD3 and expansion in IL-2, these cells are capable of mediating the regression of established tumors. In the absence of further Ag stimulation, we recently found that the down-regulation of the homing molecule L-selectin could serve as a surrogate marker for isolation of specific tumor-sensitized T cells. The L-selectin(low) (L-selectin-) T cells proliferated more vigorously than unfractionated or L-selectin(high) cells. In adoptive immunotherapy of established intracranial MCA 205 tumors, L-selectin- cells displayed at least 30-fold greater therapeutic efficacy than unfractionated cells. L-selectin(high) cells did not demonstrate any antitumor effects. Activated L-selectin- cells secreted a number of cytokines, including IFN-gamma, IL-2, IL-4, and IL-10, specifically when stimulated with cognate tumor cells. Further analysis revealed that CD4 T cells alone mediated tumor regression and secreted cytokines. Our results thus demonstrate that the purification of L-selectin...Continue Reading

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