Anticancer immune
therapies aim at the induction of
tumor-specific T cells, which ultimately should kill
tumor cells. The effector cells should, therefore, not only exert cytotoxic activity but also home to and infiltrate the
tumor site. Hence, monitoring of immune modulating
therapies should not be restricted to the circulating pool of peripheral blood mononuclear cells (PBMC) but also include tumor-infiltrating lymphocytes (TIL), as well as the correlation of these findings to the
clinical course. We report here on the longitudinal immunologic workup of a
melanoma patient who developed remarkably potent ex vivo detectable antimelanoma cytotoxic T-cell (CTL) responses after vaccinations with autologous
peptide-pulsed dendritic cells. Such potent CTL responses to multiple
tumor antigens have, to the best of our knowledge, not been described previously in
melanoma patients, neither spontaneously nor after any
therapy. This patient first experienced a transient response to
therapy but finally succumbed to
disease progression and died. Progression was associated with the decline of the numbers of
tumor-reactive T cells in circulation and at skin
metastases in addition to the loss of MHC
class I antigens. The immunologic analysis revealed that fully functional
tumor-specific T cells were present in the peripheral blood of this patient during the phase of a relatively stable disease, and in situ tetramer staining demonstrated that these cells were also accumulated at cutaneous and visceral
tumor sites. Furthermore, comparative clonotype mapping of PBMC and TIL depicted an overlapping TCR repertoire usage among these 2 compartments. Since strong CTL responses as observed in this patient are the goal of
cancer vaccination but are so far only rarely observed, the thorough analysis of patients exhibiting either exceptional clinical and/or immunologic responses appears critical to understanding how vaccine therapies work and can be further improved.