ABSTRACT
Summary MHC tetramer analysis has revealed pronounced spontaneous and therapy-induced expansions of tumor-specific T cells in cancer patients. This allows the coupling of T-cell responses to clinical course, and has, in particular for hematological malignancies, provided significant evidence for a role of these T-cell expansions in tumor control. A limitation of the currently available data is its focus on CD8 immunity, ignoring the possible contribution of CD4 T cells. However, with the increasing availability of multimeric MHC class II reagents this is likely to change in the foreseeable future. A second limitation is formed by the fact that T-cell responses have primarily been monitored in peripheral blood. The development of technology to monitor T-cell responses in small amounts of tissue material by CLSM or by other means will be essential for our understanding between T-cell immunity and clinical course for solid tumors. On a similar note, in future studies it will be important to establish not only the magnitude of (vaccine-induced) tumor-specific T-cell responses, but also the functional activity and migration of these cells, and T-cell phenotypes that correlate with this behavior. Finally, the use of MHC tetramers to selectively isolate naturally occurring or in vitro-generated TCRs may give us the tools to induce sufficiently strong tumor-specific T-cell immunity in cases in which the natural T-cell repertoire has failed.
