TY - JOUR
T1 - Adoptively transferred effector cells derived from naïve rather than central memory CD8+ T cells mediate superior antitumor immunity
AU - Hinrichs, Christian S.
AU - Borman, Zachary A.
AU - Cassard, Lydie
AU - Gattinoni, Luca
AU - Spolski, Rosanne
AU - Zhiya, Yu
AU - Sanchez-Perez, Luis
AU - Muranski, Pawel
AU - Kern, Steven J.
AU - Logun, Carol
AU - Palmer, Douglas C.
AU - Yun, Ji
AU - Reger, Robert N.
AU - Leonard, Warren J.
AU - Danner, Robert L.
AU - Rosenberg, Steven A.
AU - Restifo, Nicholas P.
PY - 2009/10/13
Y1 - 2009/10/13
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.0907448106
DO - 10.1073/pnas.0907448106
M3 - Article
C2 - 19805141
AN - SCOPUS:70350458112
SN - 0027-8424
VL - 106
SP - 17469
EP - 17474
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 41
ER -