Adoptively transferred effector cells derived from naive rather than central memory CD8+ T cells mediate superior antitumor immunity.

Published

Journal Article

Effector cells derived from central memory CD8(+) T cells were reported to engraft and survive better than those derived from effector memory populations, suggesting that they are superior for use in adoptive immunotherapy studies. However, previous studies did not evaluate the relative efficacy of effector cells derived from naïve T cells. We sought to investigate the efficacy of tumor-specific effector cells derived from naïve or central memory T-cell subsets using transgenic or retrovirally transduced T cells engineered to express a tumor-specific T-cell receptor. We found that naïve, rather than central memory T cells, gave rise to an effector population that mediated superior antitumor immunity upon adoptive transfer. Effector cells developed from naïve T cells lost the expression of CD62L more rapidly than those derived from central memory T cells, but did not acquire the expression of KLRG-1, a marker for terminal differentiation and replicative senescence. Consistent with this KLRG-1(-) phenotype, naïve-derived cells were capable of a greater proliferative burst and had enhanced cytokine production after adoptive transfer. These results indicate that insertion of genes that confer antitumor specificity into naïve rather than central memory CD8(+) T cells may allow superior efficacy upon adoptive transfer.

Full Text

Duke Authors

Cited Authors

  • Hinrichs, CS; Borman, ZA; Cassard, L; Gattinoni, L; Spolski, R; Yu, Z; Sanchez-Perez, L; Muranski, P; Kern, SJ; Logun, C; Palmer, DC; Ji, Y; Reger, RN; Leonard, WJ; Danner, RL; Rosenberg, SA; Restifo, NP

Published Date

  • October 13, 2009

Published In

Volume / Issue

  • 106 / 41

Start / End Page

  • 17469 - 17474

PubMed ID

  • 19805141

Pubmed Central ID

  • 19805141

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.0907448106

Language

  • eng

Conference Location

  • United States