Pr. Dunbar et al., A shift in the phenotype of melan-A-specific CTL identifies melanoma patients with an active tumor-specific immune response, J IMMUNOL, 165(11), 2000, pp. 6644-6652
In a significant proportion of melanoma patients, CTL specific for the mela
n-A(26/7-35) epitope can be detected in peripheral blood using HLA-A2/pepti
de tetramers, However, the functional capacity of these CTL has been contro
versial, since although they prove to be effective killers after in vitro e
xpansion, in some patients they have blunted activation responses ex vivo.
We used phenotypic markers to characterize melan-A tetramer(+) cells in bot
h normal individuals and melanoma patients, and correlated these markers wi
th ex vivo assays of CTL function. Melanoma patients with detectable melan-
A tetramer(+). cells in peripheral blood fell into two groups. Seven of thi
rteen patients had a CCR7(+) CD45R0(-) CD45RA(+) phenotype, the same as tha
t found in some healthy controls, and this phenotype was associated with a
lack of response to melan-A peptide ex vivo. In the remaining six patients,
melan-A tetramer+ cells were shifted toward a CCR7(-) CD45R0(+) CD45RA(-)
phenotype, and responses to melan-A peptide could be readily demonstrated e
x vivo. When lymph nodes infiltrated by melan-A-expressing melanoma cells w
ere examined, a similar dichotomy emerged. These findings demonstrate that
activation of melan-A-specific CTL occurs in only some patients with malign
ant melanoma, and that only patients with such active immune responses are
capable of responding to Ag in ex vivo assays.