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

作者：Hinrichs Christian S; Borman Zachary A; Cassard Lydie; Gattinoni Luca; Spolski Rosanne; Yu Zhiya; Sanchez Perez Luis; Muranski Pawel; Kern Steven J; Logun Carol; Palmer Douglas C; Ji Yun; Reger Robert N; Leonard Warren J; Danner Robert L; Rosenberg Steven A; Restifo Nicholas P^*

来源：Proceedings of the National Academy of Sciences, 2009, 106(41): 17469-17474.

DOI：10.1073/pnas.0907448106

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 naive T cells. We sought to investigate the efficacy of tumor-specific effector cells derived from naive 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 naive, rather than central memory T cells, gave rise to an effector population that mediated superior antitumor immunity upon adoptive transfer. Effector cells developed from naive 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, naive-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 naive rather than central memory CD8( ) T cells may allow superior efficacy upon adoptive transfer.

• 出版日期2009-10-13